Preventive and therapeutic effects of Babaodan on hepatic encephalopathy in rats with acute liver failure
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摘要:
目的探讨八宝丹对急性肝衰竭大鼠肝性脑病的防治作用及机理。方法将50只Wistar大鼠随机分为5组,即正常组、模型组、八宝丹低剂量组、八宝丹高剂量组和乳果糖组。各治疗组每天予以相应药物灌胃1次,正常组和模型组予以同体积0. 3%的羧甲基纤维素钠;灌胃第4天,以硫代乙酰胺(350 mg/kg)腹腔注射诱导肝性脑病,正常组注射等体积生理盐水,每24 h注射1次,共注射3次进行造模,造模后12 h,处死大鼠。HE染色观察肝和脑组织的病理变化,试剂盒检测血氨和肝功能指标,RT-PCR法检测肝组织和脑组织的基因变化。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果与模型组比较,八宝丹低剂量组和高剂量组的血氨、TBil、TBA、ALT和AST水平均明显降低(P值均<0. 05),TP水平明显升高(P值均<0. 05),八宝丹高剂量组的Alb水平明显升高(P <0. 05)。八宝丹低剂量组和高剂量组肝组织的坏死、炎症均显著改善,脑组织的坏死、核固缩减轻。与模型组相比,八宝丹低剂量组和高剂量组肝组织的TNFα、IL-1、IL-6、NF-κB、Bax、Casp...
Abstract:Objective To investigate the preventive and therapeutic effects of Babaodan on hepatic encephalopathy in rats with acute liver failure and possible mechanisms. Methods A total of 50 Wistar rats were randomly divided into normal group, model group, low-dose Babaodan group, high-dose Babaodan group, and lactulose group. The rats in the low-dose Babaodan group, the high-dose Babaodan group, and the lactulose group were given the corresponding drugs by gavage once a day, and those in the normal group and the model group were given an equal volume of 0. 3% sodium carboxymethyl cellulose. On day 4 of gavage, intraperitoneal injection of thioacetamide (350 mg/kg) was performed to induce hepatic encephalopathy, and the rats in the normal group were injected with an equal volume of normal saline, once every 24 hours for 3 times. The rats were sacrificed at 12 hours after the last injection. HE staining was used to observe pathological changes of the liver and the brain; related kits were used to measure blood ammonia and liver function parameters; RT-PCR was used to measure the changes in related genes in liver and brain tissues. The one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results Compared with the model group, the low-and high-dose Babaodan groups had significant reductions in the levels of blood ammonia, total bilirubin, total bile acid, alanine aminotransferase, and aspartate aminotransferase (all P < 0. 05) and a significant increase in total protein level (P < 0. 05) , and the high-dose Babaodan group had a significant increase in albumin (P < 0. 05) . Both the low-and high-dose Babaodan groups had significant improvements in liver necrosis and inflammation and brain necrosis and karyopyknosis. Compared with the model group, the low-and high-dose Babaodan groups had significant reductions in the mRNA expression of tumor necrosis factor-α (TNF-α) , interleukin-1 (IL-1) , interleukin-6, nuclear factor-kappa B, Bax, caspase-3, and caspase-8 in liver tissue (all P < 0. 05) , and the high-dose Babaodan group had a significant increase in the mRNA expression of Bcl-2 (P < 0. 05) ; the low-and high-dose Babaodan groups also had significant reductions in the mRNA expression of IL-1, TNF-α, inducible nitric oxide synthase, and glutamine synthetase in brain tissue (all P < 0. 05) . Conclusion Babaodan can effectively regulate the expression of inflammatory factors, inhibit the apoptosis and necrosis of hepatocytes, and reduce the production of blood ammonia and inflammatory infiltration, thus alleviating brain injury and exerting therapeutic effect on hepatic encephalopathy in rats with acute liver failure.
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Key words:
- hepatic encephalopathy /
- liver failure, acute /
- Babaodan /
- rats, Wistar
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[1] WENDON J, MEMBERS P, CORDOBA J, et al. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure[J]. J Hepatol, 2017, 66 (5) :1047. [2] DURAND F, NADIM MK. Management of Acute-on-Chronic Liver Failure[J]. Semin Liver Dis, 2016, 36 (2) :141-152. [3] RAKELA J, LANGE SM, LUDWIG J, et al. Fulminant hepatitis:Mayo clinic experience with 34 cases[J]. Mayo Clin Proc, 1985, 60 (5) :289-292. [4] MEHROTRA S, MEHTA N, RAO PS, et al. Live donor liver transplantation for acute liver failure:A single center experience[J]. Indian J Gastroenterol, 2018, 37 (2) :25-30. [5] ZHAO M, YE DN. Clinical observation on treatment of hepatic cirrhosis complicated with hepatic encephalopathy by integrative Chinese and Western medicine therapy[J]. Res Integr Tradit Chin West Med, 2017, 9 (1) :6-8. (in Chinese) 赵敏, 叶丹宁.中西医结合疗法救治肝硬化合并肝性脑病的临床观察[J].中西医结合研究, 2017, 9 (1) :6-8. [6] ZHANG YS, XU S, ZHAO YF, et al. Effect of Notoginseng Total glucoside on the dimethylnitrosamine induced hepatic fibrosis of rat models[J]. J Tradit Chin Med, 2011, 52 (19) :1671-1675. (in Chinese) 张永生, 徐珊, 赵育芳, 等.三七总苷对肝纤维化模型大鼠的干预作用[J].中医杂志, 2011, 52 (19) :1671-1675. [7] CHEN X, WU C, SUN RF, et al. Clinical research progress of babaodan in treatment of liver disease[J]. Chin Arch Tradit Chin Med, 2017, 35 (5) :1215-1218. (in Chinese) 陈曦, 武超, 孙润菲, 等.八宝丹治疗肝病临床研究进展[J].中华中医药学刊, 2017, 35 (5) :1215-1218. [8] DING J, ZHANG Y, WU R, et al. Study on specific opening effects and mechanism of musk, benzoin and styrax on blood-brain barrier brain[J]. Chin Hosp Pharm J, 2015, 35 (4) :279-282. (in Chinese) 丁洁, 张莹, 巫悦, 等.麝香、安息香和苏合香对血脑屏障脑区特异性开放作用及其机制[J].中国医院药学杂志, 2015, 35 (4) :279-282. [9] LIU PF. Clinical effect of Babaodan capsules in the treatment of jaundice type viral hepatitis[J]. Clin Res Pract, 2018, 10:138-139. (in Chinese) 刘蒲芳.八宝丹胶囊治疗黄疸型病毒性肝炎的临床效果[J].临床医学研究与实践, 2018, 10:138-139. [10] LIU Y, ZHANG L, TAN XD, et al. The therapeutic effect of combined therapy of Babaodan and ademetionine in patients with jaundice from cirrhosis[J]. Chin J Integer Trad West Med Dig, 2015, 23 (11) :773-776. (in Chinese) 刘彦, 张林, 谭旭东, 等.八宝丹联合丁二磺酸腺苷蛋氨酸治疗肝硬化合并黄疸的疗效研究[J].中国中西医结合消化杂志, 2015, 23 (11) :773-776. [11] TERBLANCHE J, HICKMAN R. Animal models of fulminant hepatic failure[J]. Dig Dis Sci, 1991, 36 (6) :770-774. [12] CHEN Q. Methodology on Chinese medicinal pharmacology[M]. Beijing:People's Medical Publishing House, 2011:1261-1263. (in Chinese) 陈奇.中药药理研究方法学[M].北京:人民卫生出版社, 2011:1261-1263. [13] CHEN LW, XU SQ, FU J. Application study of death education intervention from the perspective of the meaning of life in the care of patients with advanced hepatic cancer accompanied with hepatic encephalopathy[J]. Chin Mod Doct, 2016, 54 (19) :149-153. (in Chinese) 陈乐微, 徐胜前, 富静.基于生命意义角度的死亡教育干预在晚期肝癌并发肝性脑病患者护理中的应用研究[J].中国现代医生, 2016, 54 (19) :149-153. [14] YANG N, LIU H, JIANG Y, et al. Lactulose enhances neuroplasticity to improve cognitive function in early hepatic encephalopathy[J]. Neural Regen Res, 2015, 10 (9) :1457-1462. [15] LI Y, ZHANG J, XU P, et al. Acute liver failure impairs function and expression of breast cancer resistant protein (BCRP) at rat bloodbrain barrier partly via ammonia-ROS-ERK1/2 activation[J]. J Neurochem, 2016, 138 (2) :282-294. [16] SALEH DO, ABDEL JALEEL GA, ELAWDAN SA, et al. Thioacetamide-induced liver injury:Protective role of genistein[J]. Can J Physiol Pharmacol, 2014, 92 (11) :965-973. [17] LUO M, DONG L, LI J, et al. Protective effects of pentoxifylline on acute liver injury induced by thioacetamide in rats[J]. Int J Clin Exp Pathol, 2015, 8 (8) :8990-8996. [18] SIDDIQUI WA, AHAD A, AHSAN H. The mystery of BCL2 family:Bcl-2 proteins and apoptosis:An update[J]. Arch Toxicol, 2015, 89 (3) :289-317. [19] KVANSAKUL M, HINDS MG. The Bcl-2 family:Structures, interactions and targets for drug discovery[J]. Apoptosis, 2015, 20 (2) :136-150. [20] GREEN DR, LLAMBI F. Cell death signaling[J]. Cold Spring Harb Perspect Biol, 2015, 7 (12) :a006080. [21] FLUSBERG DA, SORGER PK. Surviving apoptosis:Life-death signaling in single cells[J]. Trends Cell Biol, 2015, 25 (8) :446-458. [22] LBRECHT J, JONES EA. Hepatic encephalopathy:Molecular mechanisms underlying the clinical syndrome[J]. J Neurol Sci, 1999, 170 (2) :138-146. [23] CHU CJ, CHANG CC, WANG TF, et al. Detrimental effects of nitric oxide inhibition on hepatic encephalopathy in rats with thioacetamide-induced fulminant hepatic failure:Role of nitric oxide synthase isoforms[J]. J Gastroenterol Hepatol, 2006, 21 (7) :1194-1199. [24] SUAREZ I, BODEGA G, RUBIO M, et al. Induction of NOS and nitrotyrosine expression in the rat striatum following experimental hepatic encephalopathy[J]. Metab Brain Dis, 2009, 24 (3) :395-408. [25] SUN RF, WU C, CHEN X, et al. Research advances in integrated traditional Chinese and Western medicine diagnosis and treatment of minimal hepatic encephalopathy[J]. J Clin Hepatol, 2016, 32 (9) :1801-1805. (in Chinese) 孙润菲, 武超, 陈曦, 等.轻微肝性脑病的中西医诊疗进展[J].临床肝胆病杂志, 2016, 32 (9) :1801-1805.
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