蓝莓联合益生菌通过IL-22调控的JAK1/STAT3/BAX通路改善非酒精性脂肪性肝病的作用机制

祝娟娟; 程明亮; 赵雪珂; 穆茂

doi:10.3969/j.issn.1001-5256.2018.09.022

蓝莓联合益生菌通过IL-22调控的JAK1/STAT3/BAX通路改善非酒精性脂肪性肝病的作用机制

DOI: 10.3969/j.issn.1001-5256.2018.09.022

贵州医科大学附属医院感染科

基金项目:

贵州省科技计划项目(黔科合支撑[2017]2874)；贵阳市科技局联合基金项目(筑科合同[2018]1-92)；贵州省卫生计生委科学技术基金项目(gzwjkj2016-1-023)；

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中图分类号: R575.5
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出版历程
- 收稿日期: 2018-04-02
- 出版日期: 2018-09-20

Mechanism of action of blueberry combined with probiotics in improving nonalcoholic fatty liver disease by affecting the JAK1/STAT3/BAX signaling pathway regulated by interleukin-22

Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University

Research funding:

摘要

摘要:
目的研究蓝莓联合益生菌通过对IL-22调控的JAK1/STAT3/BAX信号通路的影响,进一步探明其改善非酒精性脂肪性肝病（NAFLD）的作用机制。方法清洁级SD大鼠40只分为正常对照组（CG）、IL-22siRNA阴性对照组（IL-22SI-NC）、IL-22siRNA组（IL-22SI）、IL-22siRNA阴性对照+蓝莓益生菌组（IL-22SI-NC+BPG）、IL-22siRNA+蓝莓益生菌组（IL-22SI+BPG）。正常对照组予100%普通饮食,其余大鼠均采用复合高脂饲料制备脂肪肝模型,同时予IL-22siRNA阴性对照慢病毒及IL-22siRNA慢病毒腹部肝区注射（盲穿）,隔日1次,共12周,取肝脏确认造模及siRNA封闭效果后予蓝莓益生菌原液灌胃,同时按上述分组后给予正常饮食,予蓝莓益生菌原液灌胃,共观察8周。多组间比较采用单因素方差分析,进一步比较方差齐时采用SNK法（q检验）,方差不齐时用Tamhane法（q’检验）。结果 IL-22SI组与IL-22SI-NC组比较,ALT、AST、TC、TG、LDL均显著升高（P值均<0.01）,HDL显著降低（P<...
- 非酒精性脂肪性肝病 /
- 白细胞介素10 /
- 有益菌种 /
- 蓝莓 /
- Janus激酶1 /
- 转录激活因子3 /
- bcl-2相关X蛋白质
Abstract:
Objective To investigate the effect of blueberry combined with probiotics on the JAK1/STAT3/BAX signaling pathway regulated by interleukin-22 (IL-22) and their mechanism of action in improving nonalcoholic fatty liver disease (NAFLD) . Methods A total of40 clean Sprague-Dawley rats were divided into normal control group (CG group) , IL-22 siRNA-negative control group (IL-22 SI-NC group) , IL-22 siRNA group (IL-22 SI group) , IL-22 siRNA-negative control + blueberry-probiotics group (IL-22 SI-NC + BPG group) , and IL-22 siRNA + blueberry-probiotics group (IL-22 SI + BPG group) . The rats in the CG group were given 100% normal diet, and the rats in all the other groups were given compound high-fat diet to establish a rat model of fatty liver and were then given the injection of IL-22 siRNA-negative control lentivirus or IL-22 siRNA lentivirus at the abdominal liver area (blind puncture) every other day for 12 weeks in total. The liver was harvested to confirm whether the model was established successfully or not and the effect of siRNA, and then the above groups were given normal diet and blueberry-probiotics solution by gavage. The rats were observed for 8 weeks. One-way analysis of variance was used for comparison between multiple groups; the SNK test (q test) was used for further pairwise comparisons of data with homogeneity of variance, while the Tamhane' s test (q' test) was used for the data with heterogeneity of variance. Results Compared with the IL-22 SI-NC group, the IL-22 SI group had significant increases in alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , total cholesterol (TC) , triglyceride (TG) , and low-density lipoprotein (LDL) (all P < 0. 01) , a significant reduction in high-density lipoprotein (HDL) (P < 0. 01) , significant reductions in the mRNA and protein expression of IL-22, JAK1, and STAT3 (all P < 0. 01) , and a significant increase in the expression of Bcl-2-associated X protein (BAX) (P < 0. 01) . Compared with the IL-22 SI-NC group, the IL-22 SI-NC + BPG group had significant reductions in ALT, AST, TC, TG, and LDL (all P < 0. 01) , a significant increase in HDL (P < 0. 01) , significant increases in the mRNA and protein expression of IL-22, JAK1, and STAT3 (all P <0. 01) , and a significant reduction in BAX (P < 0. 01) . Compared with the IL-22 SI group, the IL-22 SI + BPG group had significant reductions in ALT, AST, TC, TG, and LDL (all P < 0. 05) , a significant increase in HDL (P < 0. 05) , significant increases in the mRNA and protein expression of IL-22, JAK1, and STAT3 (all P < 0. 05) , and a significant reduction in BAX (P < 0. 05) . Conclusion Blueberry combined with probiotics can antagonize hepatocyte fatty degeneration accelerated by IL-22 siRNA to a certain degree and increase the expression of IL-22, indicating that IL-22 may be a key factor for blueberry combined with probiotics in improving NAFLD. It is speculated that blueberry combined with probiotics can enhance the expression of IL-22, activate the JAK1/STAT3 signaling pathway to inhibit the expression of the downstream apoptotic factor BAX, reduce hepatocyte apoptosis, increase cholesterol metabolism, reduce lipid deposition, and thus improve NAFLD. Therefore, it is considered an adjuvant therapeutic regimen for NAFLD.
- non-alcoholic fatty liver disease /
- interleukin-10 /
- probiotics /
- blueberry /
- janus kinase 1 /
- activating transcription factor 3 /
- bcl-2-associated X protein

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参考文献(26)

[1]RAMY Y, ELISABETTA B.Should we undertake surveillance for HCC in patients with NAFLD?[J].J Hepatol, 2018, 68 (2) :326-334.

[2]HU ZJ, ZHANG J.The research status of nonalcoholic fatty liver in China[J].J Clin Hepatol, 2016, 32 (3) :552-556. (in Chinese) 胡中杰, 张晶.我国非酒精性脂肪性肝病的研究现状[J].临床肝胆病杂志, 2016, 32 (3) :552-556.

[3]HSUEH YH, CHANG YN, LOH CE, et al.AAV-IL-22 modifies liver chemokine activity and ameliorates portal inflammation in murine autoimmune cholangitis[J].J Autoimmun, 2016, 66:89-97.

[4]SHI Y, DECHUN F.Interleukin-22 in the pathogenesis and potential treatment of liver diseases[J].Liver Res, 2017, 1 (3) :181-185.

[5]ZHU JJ, CHENG ML.The expression of IL-22 in the experiment of intervention hepatocyte steatosis with blueberry probiotics serum[J].Chin Hepatol, 2016, 21 (8) :542-547. (in Chinese) 祝娟娟, 程明亮.IL-22在蓝莓益生菌血清干预肝细胞脂肪变性实验中的表达[J].肝脏, 2016, 21 (8) :542-547.

[6]ZHU J, REN T, CHENG M.The combination of bluebeery juice and probiotics reduces apoptosis of alcoholic fatty liver of mice by affecting SIRT1 pathway[J].Drug Des Devel Ther, 2016, 10:1649-1661.

[7]BRANDO J, DI C, YANG Z, et al.Intranasal administration of interferon beta attenuates neuronal apoptosis via the JAK1/STAT3/BCL-2 pathway in a rat model of neonatal hypoxic-ischemic encephalopathy[J].ASN Neuro, 2016, 8 (5) :1-14.

[8]SHIN JH, JUNG JH.Non-alcoholic fatty liver disease and flavonoids:Current perspectives[J].Clin Res Hepatol Gastroenterol, 2017, 41 (7) :17-24.

[9]MICHAEL D, GEORGIOS K, DIMITRA G, et al.Non-alcoholic fatty liver disease:An update with special focus on the role of gut microbiota[J].Metabolism, 2017, 71:182-197.

[10]ABDUL BB, JAGANATHAN K, JAYRAMAN K, et al.Blueberry inhibits invasion and angiogenesis in 7, 12-dimethylbenz[a]anthracene (DMBA) -induced oral squamous cell carcinogenesis in hamsters via suppression of TGF-βand NF-κB signaling pathways[J].J Nutr Biochem, 2016, 35:35-37.

[11]REN T, HUANG C, CHENG M.Dietary blueberry and bifidobacteria attenuate nonalcoholic fatty liver disease in rats by affecting SIRT1-mediated signaling pathway[J].Oxid Med Cell Longev, 2014, 2014:465059.

[12]OSMAN N, ADAWI D, AHRNE S, et al.Endotoxin-and D-galactosamine-induced liver injury improved by the administration of lactobacillus, bifidobacterium and blueberry[J].Dig Liver Dis, 2007, 39 (9) :849-856.

[13]FARRELL GC, CHITTURI S, LAU GK, et al.Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region:Executive summary[J].J Gastroenterol Hepatol, 2007, 22:775-777.

[14]ZENG MD, FAN JG, LU LG, et al.Guidelines for the diagnosis and treatment of nonalcoholic fatty liver diseases[J].J Dig Dis, 2008, 9:108-112.

[15]KOLANOWSKI ST, DIEKER MC, LISSENBERG SN, et al.TLR4-mediated pro-inflammatory dendritic cell differentiation in humans requires the combined action of My D88 and TRIF[J].Innate Immun, 2013, 13:105-107.

[16]CARMO RF, CAVALCANTI MSM, MOURA P, et al.Role of interleukin-22 in chronic liver injury[J].Cytokine, 2017, 98:107-114.

[17]XIAO NK, DE CF, BIN G, et al.Interleukin-22 induces hepatic stellate cell senescence and restricts liver fibrosis[J].Hepatology, 2012, 56 (3) :1150-1159.

[18]YANG L, ZHANG Y, WANG L, et al.Amelioration of high fat diet induced liver lipogenesis and hepatic steatosis by interleukin-22[J].J Hepatol, 2010, 53 (2) :339-347.

[19]XIAO NK, DE CF, STEPHANIE M, et al.Hepatoprotective and anti-fibrotic functions of interleukin-22:Therapeutic potential for the treatment of alcoholic liver disease[J].J Gastroenterol Hepatol, 2013, 28 (1) :56-60.

[20]KOBYLIAK N, BOSAK N, FALALYEYEVA T, et al.FRI-343:Effect of a probiotic on fatty liver index and liver stiffness in NAFLDpatients:Randomized clinical trial[J].J Hepatol, 2017, 66 (1) :s426-s427.

[21]NILGUN I, OZAN G.Investigation of the impact of blueberries on metabolic factors influencing health[J].J Funct Foods, 2017, 38:298-307.

[22]PATRICIO OP, GUILLERMO P, MARIA GV, et al.Impact of block cryoconcentration on polyphenol retention in blueberry juice[J].Food Biosci, 2017, 20:149-158.

[23]ZHAO XK, WU MR, YAO YM, et al.Effects of blueberry on the expression of TNF-α-R1 and SREBP-1c in acute alcoholic fatty liver[J].J Chongqing Med Univ, 2015, 20 (3) :43-46. (in Chinese) 赵雪珂, 吴荣敏, 姚玉梅, 等.蓝莓对小鼠急性酒精性脂肪肝TNF-α-R1和SREBP-1c影响的初步研究[J].重庆医科大学学报, 2015, 20 (3) :43-46.

[24]BYUN-TO, SEONG-YJ, PALANIVEL V.Probiotic-mediated blueberry (Vaccinium corymbosum L.) fruit fermentation to yield functionalized products for augmented antibacterial and antioxidant activity[J].J Biosci Bioeng, 2017, 124 (5) :542-550.

[25]SEONG-YJ, PALANIVEL V, JEONG-MK, et al.Photobiological (LED light) -mediated fermentation of blueberry (Vaccinium corymbosum L.) fruit with probiotic bacteria to yield bioactive compounds[J].LWT-Food Sci Technol, 2018, 93:158-166.

[26]REN T, ZHU J, ZHU L, CHENG M.The combination of blueberry juice and probiotics ameliorate non-alcoholic steatohepatitis (NASH) by affecting SREBP-1c/PNPLA3 pathway via PPAR alpha[J].Nutrients, 2017, 9 (198) :1-25.

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