Mechanism of action of magnolol in the treatment of acute lung injury in a rat model of severe acute pancreatitis

WANG Yan; QI WenJie; ZENG YaWei; GU PeiYun; MIAO Bin

doi:10.3969/j.issn.1001-5256.2020.12.028

Volume 36 Issue 12

Dec. 2020

Turn off MathJax

Article Contents

Abstract

References

Article Navigation > Journal of Clinical Hepatology > 2020 > 36(12): 2782-2782

PDF( 942 KB)

Mechanism of action of magnolol in the treatment of acute lung injury in a rat model of severe acute pancreatitis

DOI: 10.3969/j.issn.1001-5256.2020.12.028

Department of Infectious Diseases,Beijing Friendship Hospital,Capital Medical University
Graduate School of Capital Medical University

Research funding:

Received Date: 2020-04-29
Published Date: 2020-12-20

Abstract

Abstract

Objective To investigate the therapeutic effect of magnolol on severe acute pancreatitis( SAP) with acute lung injury from the aspect of the functional block of intestinal lymphatic circulation by magnolol. Methods A total of 30 healthy male Sprague-Dawley rats were randomly divided into sham-operation group,SAP group,and magnolol treatment group,with 10 rats in each group. The rats in the sham-operation group were given laparotomy to flip the pancreas,followed by abdominal closure; the rats in the SAP group were given retrograde pancreaticobiliary injection of 3. 75% sodium taurocholate to establish a rat model of SAP; the rats in the magnolol treatment group were given injection of magnolol 0. 2 mg/kg via the penile vein at 15 minutes before modeling. The three groups were compared in terms of pathological changes of the lung and the intestine,pathological score,the levels of D-lactic acid( DLA),diamine oxidase( DAO),high-mobility group box 1( HMGB1),receptor for advanced glycation end products( RAGE),interleukin-1β( IL-1β),interleukin-8( IL-8),interleukin-10( IL-10),and tumor necrosis factor-α( TNFα) in serum,lymphatic fluid,and tissue homogenate of the lung and the intestine,and the level of Toll-like receptor 4( TLR4) in lymphatic fluid. An analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups. Results The SAP group had congestion,edema,inflammatory cell infiltration,and bleeding in the pulmonary interstitium,and the magnolol treatment group had mild bleeding and inflammatory cell infiltration in the pulmonary interstitium,with a significantly lower degree than the SAP group. Compared with the SAP group,the magnolol treatment group had significantly lower serum levels of DAO,DLA,IL-1β,IL-8,TNFα,HMGB1,and RAGE( all P < 0. 05) and significantly lower levels of DAO,DLA,IL-1β,IL-8,TNFα,HMGB1,and RAGE in the lymphatic fluid( all P < 0. 05). Compared with the SAP group,the sham-operation group had sig-nificantly lower serum levels of DAO,DLA,IL-1β,IL-8,TNFα,HMGB1,and RAGE( all P < 0. 05) and significantly lower levels of DAO,DLA,IL-1β,IL-8,TNFα,HMGB1,and RAGE in the lymphatic fluid( all P < 0. 05). Compared with the SAP group,the magnolol treatment group had significantly lower levels of IL-1β,IL-8,TNFα,HMGB1,and RAGE in lung tissue( all P < 0. 05) and intestinal tissue( all P < 0. 05). Compared with the SAP group,the sham-operation group had significantly lower levels of IL-1β,IL-8,TNFα,HMGB1,and RAGE in lung tissue( all P < 0. 05) and intestinal tissue( all P < 0. 05). Compared with the SAP group,the magnolol treatment group and sham-operation group had a significant reduction in the protein expression of TLR4 in the lymphatic fluid( all P < 0. 05). Conclusion Magnolol can improve intestinal barrier function and alleviate lung injury in SAP by blocking intestinal lymphatic circulation,reducing the levels of inflammatory factors,and inhibiting the HMGB1-TLR4/NF-κB signal transduction pathway.
- pancreatitis,acute necrotizing,
- acute lung injury,
- MAGNOLOL,
- therapeutics

FullText(HTML)

慢性肝病的共同病理结局是肝纤维化/肝硬化。根据既往是否发生并发症，肝硬化可分为代偿期肝硬化和失代偿期肝硬化，进展至失代偿期肝硬化后，患者死亡风险增加^[1]。失代偿事件中，食管胃底静脉曲张破裂出血(esophageal variceal bleeding, EVB)尤为凶险^[2-3]。预测失代偿事件以采取积极的预防措施，是提高肝硬化患者生存期的关键。血清壳多糖酶3样蛋白1(chitinase-3-like protein 1, CHI3L1)是一种检测纤维化进展的无创指标，可预测ALT正常或轻度升高的患者中、重度肝纤维化^[4]。本研究对CHI3L1预测肝硬化患者出现失代偿事件和代偿期肝硬化患者出现首次失代偿事件风险的临床价值进行回顾性病例对照研究，探索CHI3L1对失代偿事件发生风险的评估价值，以便合理指导治疗，提高肝硬化患者生存期。

1. 资料与方法

1.1 研究对象

收集2019年1月—2021年5月于天津市第二人民医院诊疗的肝硬化患者中，符合纳排标准的患者的人口学特征、临床资料和随访1年内失代偿事件的发生情况。以随访1年内失代偿事件的发生情况进行分组，进行病例对照研究。失代偿事件定义为显性腹水、EVB或显性肝性脑病^[1]。纳入标准：(1)肝硬化诊断符合《肝硬化诊治指南》^[5]；乙型肝炎诊断符合《慢性乙型肝炎防治指南(2019年版)》^[5]；丙型肝炎诊断符合《丙型肝炎防治指南(2019年版)》^[6]；非酒精性脂肪性肝病诊断符合《非酒精性脂肪性肝病防治指南(2018更新版》^[7]；酒精性肝病符合《酒精性肝病防治指南(2018更新版)》^[8]；自身免疫性肝炎诊断符合《自身免疫性肝炎诊断和治疗指南(2021)》^[9]；原发性胆汁性胆管炎诊断符合《原发性胆汁性胆管炎的诊断和治疗指南(2021)》^[10]；(2)随访时间＞1年或随访期间发生终点事件。排除标准：(1)ALT＞2倍正常值上限；(2)合并恶性肿瘤；(3)有严重的肺心肾等系统疾病；(4)接受过降低门静脉高压的预防手段(预防性内镜套扎或硬化剂、经颈静脉肝内门体分流术或口服非选择性β受体阻滞剂)。

1.2 检测方法

血清CHI3L1水平检验采用Microlab STAR IVD ELISA全自动酶联免疫分析仪(瑞士哈美顿博纳图斯有限公司)及CHI3L1酶联免疫法检测试剂盒(杭州普望生物技术有限公司)测定；肝生化指标采用HITACHI全自动生物化学仪-7180及配套试剂(日本东京日立有限公司)测定；血常规采用Sysmex XN-2000血液分析仪及配套试剂(日本希森美康有限公司)测定；凝血指标采用STAGO Compact血凝仪及配套试剂(法国思塔高有限公司)测定。样本测定均由专职人员按照规范流程进行操作。

1.3 统计学方法

采用SPSS 28.0软件对数据进行描述和分析。采用Kolmogorov-Smirnov检验和Shapiro-Wilk检验来检验连续变量是否符合正态分布。符合正态分布的计量资料采用x±s表示，不符合正态分布采用M(P₂₅~P₇₅)，两组间比较采用成组t检验或Mann-Whitney U检验；计数资料两组间比较采用Wilcoxon秩和检验或χ²检验。采用二分类Logistic回归分析各变量与失代偿事件之间的相关性；采用受试者工作特征曲线(ROC曲线)下面积(AUC)来评价各变量对失代偿事件的预测价值，采用约登指数最大值来确定最佳临界值。P＜0.05为差异有统计学意义。

2. 结果

2.1 一般情况

本研究共纳入305例肝硬化患者，其中男176例，女129例；年龄(55.15±11.32)岁；基线时处于代偿期肝硬化患者200例，处于失代偿期肝硬化患者105例。将305例肝硬化患者，以1年内是否发生失代偿事件进行分组，发生失代偿事件组79例，未发生失代偿事件组226例；将200例代偿期肝硬化患者，以1年内是否发生首次失代偿事件进行分组，其中发生首次失代偿事件组43例，未发生首次失代偿事件组157例。两组患者基线人口学特征和临床资料均无缺失。

2.2 基线资料比较

2.2.1 1年内发生与未发生失代偿事件组间比较

发生失代偿事件组的男性占比较高、年龄较大、基线Child-Pugh分级水平较高、基线MELD评分较高、基线Alb水平较低、基线TBil水平较高、基线CHI3L1水平较高、基线INR较高且基线PLT水平较低，差异均有统计学意义(P值均＜0.05)，两组患者的病因、基线ALT水平差异均无统计学意义(表 1)。

表 1 发生与未发生失代偿事件患者基线人口学特征和临床资料的比较

Table 1. Comparison of baseline demographic characteristics and clinical data between decompensation and non-decompensation group

项目	发生失代偿事件组 (n=79)	未发生失代偿事件组 (n=226)	统计值	P值
男性[例(%)]	54(68.4)	122(54.0)	χ²=4.954	0.026
年龄(岁)	58.24±11.57	54.01±11.06	t=-2.308	0.022
病因[例(%)]			χ²=2.248	0.956
乙型肝炎	45(57.0)	115(50.9)
乙型肝炎合并NAFLD	8(10.1)	23(10.2)
丙型肝炎	9(11.4)	22(9.7)
丙型肝炎合并NAFLD	1(1.3)	6(2.7)
酒精性肝病	3(3.8)	8(3.5)
自身免疫性肝炎	2(2.5)	6(2.7)
原发性胆汁性胆管炎	1(1.3)	5(2.2)
其他	10(12.7)	41(18.1)
Child-Pugh分级[例(%)]			Z=-5.434	＜0.001
A级	30(38.0)	169(74.8)
B级	39 (49.4)	37 (16.4)
C级	10(12.7)	20(8.8)
MELD评分	9.53(7.92~12.54)	7.89(6.09~10.73)	U=6 258.500	0.001
ALT(U/L)	19.55(15.10~28.00)	22.00(16.10~29.60)	U=7 822.500	0.102
Alb(g/L)	34.40(29.10~39.90)	41.60(35.08~45.30)	U=5 040.500	＜0.001
TBil(μmol/L)	21.80(14.20~36.40)	17.65(13.30~28.03)	U=7 521.000	0.037
CHI3L1(ng/mL)	243.00(136.00~372.00)	117.50(67.75~205.25)	U=4 720.500	＜0.001
INR	1.20(1.10~1.30)	1.00(1.00~1.20)	U=5 438.000	＜0.001
PLT (×10⁹/L)	77.00(53.00~129.00)	103.50(63.75~163.00)	U=6 700.500	0.001
注：NAFLD，非酒精性脂肪性肝病。

下载: 导出CSV

| 显示表格

2.2.2 1年内发生与未发生首次失代偿事件组间比较

发生首次失代偿事件组的基线年龄较大、基线Child-Pugh分级较高、基线MELD评分较高、基线Alb水平较低、基线TBil水平较高、基线CHI3L1水平较高、基线INR较高且基线PLT水平较低，差异均有统计学意义(P值均＜0.001)；两组患者的性别、病因和基线ALT的差异均无统计学意义(表 2)。

表 2 发生与未发生首次失代偿事件患者基线人口学特征和临床资料的比较

Table 2. Comparison of baseline demographic characteristics and clinical data between first-time decompensation and non-first-time decompensation group

项目	发生首次失代偿事件组 (n=43)	未发生首次失代偿事件组 (n=157)	统计值	P值
男性[例(%)]	27(62.8)	90(57.3)	χ²=0.415	0.520
年龄(岁)	56.56±11.41	52.38±10.95	t=2.200	0.029
病因[例(%)]			χ²=4.717	0.680
乙型肝炎	23(53.5)	87(55.4)
乙型肝炎合并NAFLD	3(7.0)	20(12.7)
丙型肝炎	3(7.0)	12(7.6)
丙型肝炎合并NAFLD	1(2.3)	7(4.5)
酒精性肝病	2(4.7)	4(2.5)
自身免疫性肝炎	1(2.3)	4(2.5)
原发性胆汁性胆管炎	0(0.0)	3(1.9)
其他	10(23.3)	20(12.7)
Child-Pugh分级[例(%)]			Z=-5.510	＜0.001
A级	29(67.4)	151(96.2)
B级	14(32.6)	5(3.2)
C级	0(0.0)	1(0.6)
MELD评分	9.39(7.47~12.30)	6.78(5.60~8.87)	U=1 804.000	＜0.001
ALT(U/L)	19.00(15.10~26.30)	22.00(16.00~28.40)	U=2 873.000	0.135
Alb(g/L)	37.30(30.50~44.30)	43.30(39.75~46.30)	U=1 898.000	＜0.001
TBil(μmol/L)	27.53(14.70~35.00)	15.60(12.10~21.25)	U=2 236.500	＜0.001
CHI3L1(ng/mL)	227.98(110.00~314.00)	90.00(58.00~168.50)	U=1 681.500	＜0.001
INR	1.16(1.00~1.30)	1.00(0.90~1.10)	U=1 716.500	＜0.001
PLT(×10⁹/L)	83.26(44.00~100.00)	123.00(85.00~174.50)	U=1 631.000	＜0.001

下载: 导出CSV

| 显示表格

2.3 二分类Logistic回归分析

2.3.1 以1年内发生失代偿事件为结局进行二分类Logistic回归分析

单因素回归分析中，患者的年龄、性别、基线Child-Pugh分级、MELD评分、Alb水平、CHI3L1水平、INR和PLT水平是患者1年内发生失代偿事件的影响因素(P值均＜0.05)(表 3)。将以上因素纳入多因素回归分析，结果显示基线Child-Pugh分级(OR=1.722, 95%CI：1.151~2.577，P=0.008)和CHI3L1水平(OR=1.004, 95%CI：1.002~1.006，P＜0.001)均为患者1年内发生失代偿事件的独立影响因素。

表 3 肝硬化患者1年内发生失代偿事件的单因素分析

Table 3. Univariate analysis of factors associated with decompensated events in patients with cirrhosis

变量	OR(95%CI)	P值
年龄	1.035(1.010~1.060)	0.005
性别	0.543(0.316~0.933)	0.027
Child-Pugh分级	2.328(1.608~3.372)	＜0.001
MELD评分	1.111(1.041~1.187)	0.002
ALT	0.983(0.960~1.007)	0.161
Alb	0.898(0.864~0.933)	＜0.001
TBil	1.003(0.994~1.012)	0.508
CHI3L1	1.005(1.003~1.007)	＜0.001
INR	15.077(4.035~56.336)	＜0.001
PLT	0.995(0.991~0.999)	0.026

下载: 导出CSV

| 显示表格

2.3.2 以1年内发生首次失代偿事件为结局进行二分类Logistic回归分析

单因素回归分析中，患者的年龄、基线Child-Pugh分级、MELD评分、Alb水平、TBil水平、CHI3L1水平、INR和PLT水平是患者1年内发生首次失代偿事件的影响因素(P值均＜0.05)(表 4)。将以上因素纳入多因素回归分析，结果显示基线Child-Pugh分级(OR=7.184, 95%CI：2.573~ 20.056，P＜0.001)和CHI3L1水平(OR=1.006, 95%CI：1.003~1.008，P＜0.001) 均为患者1年内发生首次失代偿事件的独立影响因素。

表 4 代偿期肝硬化患者1年内发生首次失代偿事件的单因素分析

Table 4. Univariate analysis of factors associated with first decompensated events in patients with compensatory cirrhosis

变量	OR(95%CI)	P值
年龄	1.035(1.003~1.069)	0.031
性别	0.796(0.397~1.594)	0.520
Child-Pugh分级	8.831(3.284~23.746)	＜0.001
MELD评分	1.288(1.146~1.446)	＜0.001
ALT	0.972(0.935~1.010)	0.143
Alb	0.871(0.820~1.924)	＜0.001
TBil	1.027(1.006~1.049)	0.012
CHI3L1	1.006(1.003~1.009)	＜0.001
INR	192.611(17.328~2 140.935)	＜0.001
PLT	0.984(0.976~0.991)	＜0.001

下载: 导出CSV

| 显示表格

2.4 预测效能评估

对于肝硬化患者，以1年内失代偿事件的发生情况为状态变量，以CHI3L1为检验变量，绘制ROC曲线。结果显示AUC为0.736(95%CI：0.673~0.798，P＜0.001)，最佳临界值为206.5 ng/mL时，敏感度和特异度分别为62.0%和76.1%(图 1a)。以CHI3L1为检验变量，分别预测1年内腹水、EVB和显性肝性脑病发生风险的AUC(表 5)。

图 1 CHI3L1、Child-Pugh分级和预测模型的ROC曲线

注：a, 失代偿事件；b，首次失代偿事件。

Figure 1. ROC curve of CHI3L1, Child Pugh classification and the model for the prediction

下载: 全尺寸图片幻灯片

表 5 血清CHI3L1水平对各失代偿事件的预测价值

Table 5. Predictive value of serum CHI3L1 level for decompensated events in patients with cirrhosis

变量	AUC	95%CI	截断值(ng/mL)	敏感度(%)	特异度(%)	阳性预测值(%)	阴性预测值(%)
腹水	0.726	0.660~0.792	206.5	63.2	74.7	41.7	87.6
EVB	0.824	0.760~0.888	215.5	78.3	76.8	37.5	95.2
显性肝性脑病	0.515	0.394~0.576	102.5	100	61.1	2.1	100

下载: 导出CSV

| 显示表格

对于代偿期肝硬化患者，以1年内首次失代偿事件的发生情况为状态变量，以血清CHI3L1水平为检验变量，绘制ROC曲线。结果显示AUC为0.751(95%CI：0.671~0.831，P＜0.001)，最佳临界值为95.5 ng/mL时，敏感度和特异度分别为90.7%和55.4%；以Child-Pugh分级为检验变量，绘制ROC曲线。结果显示AUC为0.643(95%CI：0.538~0.746，P=0.004)。联合Child-Pugh分级和CHI3L1为检验变量建立预测模型，Logit(P)=-4.492+0.006×CHI3L1+1.972×Child-Pugh分级，得到的Logit模型具有统计学意义(χ²=36.855，P＜0.001)；绘制ROC曲线，结果显示AUC为0.809(95%CI：0.737~0.882，P＜0.001)，该模型能够正确分类82.0%的研究对象，约登指数最大时敏感度和特异度分别为72.1%和77.1%(图 1b)。

3. 讨论

CHI3L1是一种含383个氨基酸的单体糖基化蛋白，分子量约40 kD。编码CHI3L1的基因位于人染色体1q32.1的一个8 kb的DNA上。CHI3L1由包括肝巨噬细胞在内的多种类型的细胞以不同模式分泌，与血管生成、炎症反应、组织重塑和纤维化进展等多种病理过程有关，可通过激活TGF-β1、MAPK、ERK和PI3K/AKT等信号通路来发挥作用，但其在疾病进展中确切的作用机制暂未完全明确^[11]。CHI3L1在肝硬化的病程中可通过抑制肝巨噬细胞的凋亡来加剧肝硬化的进程，在肝病领域，现阶段针对CHI3L1的研究主要集中在对肝纤维化/肝硬化程度和对肝癌发生风险的预测^[12]，这一指标还未被用于对肝硬化患者失代偿事件发生风险的预测。本研究尝试使用CHI3L1对代偿期肝硬化患者发生失代偿事件的风险和对代偿期肝硬化患者发生首次失代偿事件的风险进行预测。

肝硬化患者的中位生存期约12年，发生首次失代偿事件后，中位生存期约2年^[13]。为提高肝硬化患者的生存期，需要预测失代偿事件以采取积极的预防措施。笔者团队^[14]联合血小板和使用瞬时弹性成像检查测得的肝硬度数据建立了预测首次失代偿事件发生风险的模型，但是这一模型涉及的瞬时弹性成像检查在很多地区暂未开展，这一模型还未在临床普及应用。本研究发现，将患者血清CHI3L1用于对首次失代偿事件的预测时，AUC为0.751；反映肝脏储备功能的Child-Pugh分级所包含的多项指标是肝硬化患者发生失代偿事件的重要影响因素，将血清CHI3L1与Child-Pugh分级进行联合建立的预测模型，AUC可达0.809，具有一定的临床应用价值，为预测首次失代偿事件提供了新的可选手段。

失代偿事件中，EVB可危及生命。我国的《肝硬化门静脉高压食管胃静脉曲张出血的防治指南》^[15]建议结合胃镜和Child-Pugh分级来判断肝硬化患者EVB的风险，以决定进一步的预防和治疗方案。但胃镜属于侵入性检查，患者接受程度较差，且长期随访困难。作为现阶段临床关注的焦点，很多研究在探索可用于对肝硬化患者发生EVB风险进行预测的模型，但现有的模型存在应用病因范围狭窄和涉及的侵入性检查难以用于随访等诸多问题，仍有必要进行进一步研究^[16-17]。血清学指标相对易获得，本研究使用血清CHI3L1对肝硬化患者发生EVB的风险进行预测时，AUC为0.824, 可用于对肝硬化患者发生EVB风险进行非侵入性的评估，以便针对性地指导肝硬化患者的预防和治疗方案。

综上，本研究纳入了多种病因导致肝硬化的患者共305例，结合患者1年的随访数据，发现血清CHI3L1拥有无创评估肝硬化患者发生首次失代偿事件这一显著影响生存期事件的风险的前景，可作为针对代偿期肝硬化患者预测首次失代偿事件的预测因子。且对于代偿期肝硬化人群发生EVB的风险已具有较好的预测价值，具有较好的临床应用前景。本研究为单中心回顾性研究，由于回顾性和病因构成复杂而存在偏倚问题，需要进一步在外部队列中进行验证。但是本研究所使用的血清学指标方便获得，可重复性强，且避免了影像学检查所存在的主观因素影响。同时作为使用试剂盒即可进行检测的方案，成本较低，易于推广。尤其在瞬时弹性成像检查还未开展的地区，迫切需要一些利于随访的血清学指标^[18]。门静脉高压是肝硬化患者发生失代偿事件的主要驱动因素^[19]，新生血管的生成在门静脉高压的发生和发展中起至关重要的作用^[20]。CHI3L1参与血管生成的病理进程^[10]，考虑其血清学水平可能反映了肝硬化患者门静脉高压的进展程度，进而实现了对患者发生失代偿事件风险的预测效能，但具体机制仍待基础实验和进一步临床研究探索。

References(21)

References

[1] RENNER IG,SAVAGE WT 3rd,PANTOJA JL,et al. Death due to acute pancreatitis. A retrospective analysis of 405 autopsy cases[J]. Dig Dis Sci,1985,30(10):1005-1018.

[2] STEER ML. Relationship between pancreatitis and lung diseases[J]. Respir Physiol,2001,128(1):13-16.

[3] WANG D,LI Y,FAN LQ,et al. Expression and significance of NF-kB,IL-6 and TNF-αin liver injury interfered by thoracic duct drainage of severe acute pancreatitis[J]. J Hebei Med Univ,2010,31(8):905-908.(in Chinese)王冬，李勇，范立侨，等．大鼠重症急性胰腺炎肝损伤经胸导管引流干预时NF-κB、IL-6、TNF-α的表达及意义[J]．河北医科大学学报，2010,31(8):905-908.

[4] WANG HM,ZHANG SW. Research progress of magnolol pharmacology[J]. Beijing J Tradit Chin Med,2009,28(7):562-565.(in Chinese)王海曼，张淑文．厚朴酚药理作用的研究进展[J]．北京中医药，2009,28(7):562-565.

[5] MIAO B,ZHANG SW,WANG H,et al. Magnolol pretreatment prevents sepsis-induced intestinal dysmotility by maintaining functional interstitial cells of Cajal[J]. J Capit Med Univ,2013,34(2):163-170.(in Chinese)苗彬，张淑文，王红，等．Cajal细胞在脓毒症所致胃肠动力障碍中的形态改变及厚朴酚干预的实验研究[J]．首都医科大学学报，2013,34(2):163-170.

[6] ZHANG YL,YUAN WH,XU M,et al. The role of cold-inducible RNA-Binding protein(CIRP)in early liver damage of severe acute pancreatitis with secondary infection[J]. Chin J Dig,2011,31(5):330-334.(in Chinese)．张尤历，袁伟红，徐岷，等．重症急性胰腺炎继发感染早期肝损伤时髓样细胞表达激发受体-1的诊断价值[J]．中华消化杂志，2011,31(5):330-334.

[7] FENG SY. Rhubarb to prevent gastrointestinal failure[J]. Chin J Integr Trad West Med,2000,20(10):795-797.(in Chinese)冯顺友．大黄防治胃肠功能衰竭[J]．中国中西医结合杂志，2000,20(10):795-797.

[8] YE ML,PENG Y. Research advance in the mechanism of intestinal motility disorders in patients with severe acute pancreatitis[J]. Med Recapitul,2016,22(20):4039-4042.(in Chinese)．叶美玲，彭燕．急性重症胰腺炎肠道动力障碍机制的研究进展[J]．医学综述，2016,22(20):4039-4042.

[9] ZHANG Y,TANG F. Advance in latest studies on pharmacological effects of magnolol[J]. China J Chin Mater Med,2012,37(23):3526-3530.(in Chinese)张勇，唐方．厚朴酚药理作用的最新研究进展[J]．中国中药杂志，2012,37(23):3526-3530.

[10] QIN C,DAI X,YANG XQ,et al. Intervention effect of honokiol on inflammatory response in lung tissue of asthma mice and its mechanism[J]. J Jilin Univ(Med Edit),2020,46(2):214-220,431.(in Chinese)秦超，戴曦，杨小琼，等．和厚朴酚对哮喘小鼠肺组织炎症反应的干预作用及其机制[J]．吉林大学学报(医学版)，2020,46(2):214-220,431.

[11] DUAN JQ,LIN Y,ZHAO QF,et al. The protective effect and mechanism of magnolol on acute lung injury in sepsis rat model[J]. Chin J Gerontol,2018,38(11):2745-2747.(in Chinese)段金旗，林艳，赵芹芳，等．厚朴酚对脓毒症大鼠模型急性肺损伤的保护作用及机制[J]．中国老年学杂志，2018,38(11):2745-2747.

[12] SEELY AJ,NAUD JF,CAMPISI G,et al. Alteration of chemoattractant receptor expression regulates human neutrophil chemotaxis in vivo[J]. Ann Surg,2002,235(4):550-559.

[13] PASZKOWSKI AS,RAU B,MAYER JM,et al. Therapeutic application of caspase 1/interleukin-1beta-converting enzyme inhibitor decreases the death rate in severe acute experimental pancreatitis[J]. Ann Surg,2002,235(1):68-76.

[14] LIU ZY,FEI H,LIU J,et al. The role of daphnetin pretreatment on histopathologic changes and serum IL-6,IL-10 levels in a-cute pancreatitis rats[J]. Chin J Microcirc,2016,26(2):1-4,85.(in Chinese)刘志勇，费浩，刘娇，等．瑞香素预处理对急性胰腺炎大鼠组织病理变化和白细胞介素-6、白细胞介素-10水平的作用[J]．微循环学杂志，2016,26(2):1-4,85.

[15] SONG RB,MA JT. Regulation of IL-10 on inflammation-related cytokines in severe pancreatitis in rats[J]. Hebei Med J,2009,31(12):1451-1452.(in Chinese)宋润波，马建亭．IL-10对大鼠重症胰腺炎炎症相关细胞因子的调节作用[J]．河北医药，2009,31(12):1451-1452.

[16] LI L,YU J,MU R,et al. Clinical effect of electroacupuncture on lung injury patients caused by severe acute pancreatitis[J]. Evid Based Complement Alternat Med,2017,2017:3162851.

[17] ZHANG G,LIU XB,HU WM. Relationship between TNFαgene expression and lung injury in the lungs of acute pancreatitis rats[J]. World Chin J Dig,2000,8(2):142.(in Chinese)．张刚，刘续宝，胡伟明．急性胰腺炎大鼠肺内TNFα基因表达与肺损伤的关系[J]．世界华人消化杂志，2000,8(2):142.

[18] LU HH,SHI Z,LIU B,et al. Effects of TNFα，IL-1,IL-6 in acute pancreatitis-associated acute lung injury[J].Chongqing Med,2007,36(18):1818-1819.(in Chinese)陆海华，史忠，刘波，等．急性胰腺炎相关性肺损伤患者早期血清TNFα、IL-1、IL-6的变化及其临床意义[J]．重庆医学，2007,36(18):1818-1819.

[19] WANG M,WANG B. HMGB1 of sepsis biomarkers and drug target of traditional Chinese medicine[J]. Jilin J Tradit Chin Med,2018,38(4):494-496.(in Chinese)王淼，王兵．HMGB1作为脓毒症生物标记物与中药药物靶点的研究进展[J]．吉林中医药，2018,38(4):494-496.

[20] WANG J,HUANG Z,WEI W,et al. The expression of HMGB1 in lung injury and the effect of ulinastatin on rats with severe acute pancreatitis[J]. Med J West China,2018,30(2):174-177,181.(in Chinese)．王静，黄忠，魏尉，等．HMGB1在重症急性胰腺炎大鼠肺损伤中的表达及乌司他丁的干预效应[J]．西部医学，2018,30(2):174-177,181.

[21] SIMS GP,ROWE DC,RIETDIJK ST,et al. HMGB1 and RAGE in inflammation and cancer[J]. Annu Rev Immunol,2010,28:367-388.

Relative Articles

[1]	Yi BAI, Jinming LI, Yamin ZHANG. An excerpt of European Society for Organ Transplantation consensus statement on biomarkers in liver transplantation （2023）[J]. Journal of Clinical Hepatology, 2024, 40(2): 252-257. doi: 10.12449/JCH240206
[2]	Jiang LI, Xing DAI, Dazhi TIAN, Wentao JIANG, Zhongyang SHEN. Advances in the clinical research on liver transplantation in treatment of acute-on-chronic liver failure[J]. Journal of Clinical Hepatology, 2022, 38(5): 1188-1191. doi: 10.3969/j.issn.1001-5256.2022.05.045
[3]	Nengli WANG, Xinbao XIE. Liver transplantation for pediatric acute liver failure[J]. Journal of Clinical Hepatology, 2022, 38(2): 278-281. doi: 10.3969/j.issn.1001-5256.2022.02.006
[4]	Xiaopeng DING, Jun TIE, Jiahao YU, Pengwei REN, Guoyun XUAN, Shuoyi MA, Changcun GUO, Ying HAN, Xinmin ZHOU. Efficacy and safety of programmed death-1 inhibitor combined with transarterial chemoembolization and anti-angiogenic drugs in treatment of advanced hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2022, 38(5): 1086-1091. doi: 10.3969/j.issn.1001-5256.2022.05.021
[5]	Qian LU, Xuan TONG, Rui TANG. Advances in conversion therapy strategies for liver transplantation for liver cancer[J]. Journal of Clinical Hepatology, 2021, 37(2): 257-259. doi: 10.3969/j.issn.1001-5256.2021.02.003
[6]	Zhao LI, Jiye ZHU. Liver transplantation for liver cancer in the era of immunotherapy[J]. Journal of Clinical Hepatology, 2021, 37(2): 249-252. doi: 10.3969/j.issn.1001-5256.2021.02.001
[7]	Chengzuo HAN, Qiang WEI, Xiao XU. Transplant oncology creates a new era of liver transplantation for the treatment of liver cancer[J]. Journal of Clinical Hepatology, 2021, 37(2): 253-256. doi: 10.3969/j.issn.1001-5256.2021.02.002
[8]	Ha FuShuang, Han Tao, Tang Fei, Yan JunQing, Wang HaoYu. Predictive factors for the clinical effect of PD-1/PD-L1 checkpoint inhibitors in treatment of hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2020, 36(6): 1389-1392. doi: 10.3969/j.issn.1001-5256.2020.06.044
[9]	Zhang HongTao, Tao KaiShan. Liver transplantation for the treatment of intrahepatic cholangiocarcinoma: Controversies and perspectives[J]. Journal of Clinical Hepatology, 2019, 35(12): 2644-2647. doi: 10.3969/j.issn.1001-5256.2019.12.006
[10]	Zhang DaLi, Gao YinJie, Feng DanNi, Zhang LiJuan, He Xi, Liu ZhenWen, Liu HongLing. A case of Pneumocystis carini pneumonia after liver transplantation[J]. Journal of Clinical Hepatology, 2019, 35(2): 384-385. doi: 10.3969/j.issn.1001-5256.2019.02.030
[11]	Ye HaiWen, Zhou Ying, Lu Qian, Zhang LingQiang, Deng Yong, Xu XiaoLei, Li XiaoWen, Jia Fan, Wang HaiJiu, Fan HaiNing. Small-for-size syndrome in hepatic alveolar echinococcosis treated by ex vivo liver resection and autotransplantation: A case report [J]. Journal of Clinical Hepatology, 2019, 35(4): 858-860. doi: 10.3969/j.issn.1001-5256.2019.04.030
[12]	Xu Hui, Li Bing. Research advances in endoscopic treatment of biliary complications after liver transplantation[J]. Journal of Clinical Hepatology, 2018, 34(10): 2245-2250. doi: 10.3969/j.issn.1001-5256.2018.10.041
[13]	Zheng WeiPing, Song HongLi, Shen ZhongYang. An excerpt of 2018 BTS guidelines for hepatitis B & solid organ transplantation (first edition)[J]. Journal of Clinical Hepatology, 2018, 34(8): 1649-1653. doi: 10.3969/j.issn.1001-5256.2018.08.011
[14]	Ding YiTao. Bioartificial liver and liver transplantation: new modalities for the treatment of liver failure[J]. Journal of Clinical Hepatology, 2017, 33(9): 1693-1698. doi: 10.3969/j.issn.1001-5256.2017.09.013
[15]	Mao JiaXi, Zou You, Guo WenYuan. Clinical effect of liver transplantation in the treatment of hepatolenticular degeneration[J]. Journal of Clinical Hepatology, 2017, 33(10): 1977-1980. doi: 10.3969/j.issn.1001-5256.2017.10.026
[16]	Liu Bo, Liu YingDi, Sun GuoHui, Jiang Hua, Wang Juan, Sun Xiao, Shen ShaoHua, Li Meng, Fu LaiLin. Endoscopic therapy for gastrointestinal bleeding after liver transplantation[J]. Journal of Clinical Hepatology, 2016, 32(10): 1964-1966. doi: 10.3969/j.issn.1001-5256.2016.10.030
[17]	Yang Yang, Deng YiNan. Application of immune induction therapy with antibodies in liver transplantation[J]. Journal of Clinical Hepatology, 2015, 31(12): 2031-2034. doi: 10.3969/j.issn.1001-5256.2015.12.010
[18]	Liu JianYong, Cai QiuCheng, Jiang Yi. Clinical effects of comprehensive treatment and liver transplantation for hepatocellular carcinoma exceeding Milan criteria: a comparative study[J]. Journal of Clinical Hepatology, 2014, 30(9): 913-916. doi: 10.3969/j.issn.1001-5256.2014.09.019
[19]	Lu: GuoYue, Qiu Wei. Clinical progress in donation after cardiac death liver transplantation in China[J]. Journal of Clinical Hepatology, 2014, 30(1): 11-13. doi: 10.3969/j.issn.1001-5256.2014.01.004
[20]	Hao WeiGang, Duan LiPing, Zhang HaiRong. Orthotopic liver transplantation treats hepatic vein occlusion disease: a case report[J]. Journal of Clinical Hepatology, 2011, 27(2): 205-205.

Supplements(0)

Cited By

Cited by

Periodical cited type(5)

1.	刘平箕，姚黎超，胡雪，王铮，熊芷玉，江应安. 人脐带间充质干细胞（hUC-MSC）对肝纤维化小鼠模型的治疗作用及其机制分析. 临床肝胆病杂志. 2024(03): 527-532 . 本站查看
2.	谭梅傲，黄祎，刘姝婉，王雅楠，刘华宝. 基于“肝为气之治”理论探讨肝硬化全病程中医防治机理及实践. 中西医结合肝病杂志. 2024(04): 292-295+300 .
3.	杨宁，折慧，屈文静，何学学. 血清HBD-1、CHI3L1水平在乙型肝炎病毒感染相关慢加急性肝衰竭预后预测中的效能. 山东医药. 2024(28): 1-6 .
4.	李晓宇，黄秀香，叶迎宾. 血清壳多糖酶3样蛋白1和PLT的比值与FIB-4指数在慢性乙型肝炎轻、中度诊断效价的比较. 标记免疫分析与临床. 2024(09): 1693-1697 .
5.	黄滨宁. 乙型肝炎肝硬化患者血清LN、HA、CⅣ、PⅢ、CHI3L1水平对肝纤维化程度的评估价值. 中国医药指南. 2024(34): 37-39 .

Other cited types(0)

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Get Citation

PDF

XML

Article Metrics

Article views (4009) PDF downloads(67)

Mechanism of action of magnolol in the treatment of acute lung injury in a rat model of severe acute pancreatitis

DOI: 10.3969/j.issn.1001-5256.2020.12.028