生长抑素通过抑制内质网应激反应减轻肝纤维化小鼠肝损伤研究

doi:10.3969/j.issn.1672-5069.2021.02.006

Abstract

Abstract: Objective The aim of this study was to observe the effects of somatostatin (SST) on the inflammatory response and apoptosis in mice with CCl₄-induced liver fibrosis (LF) , and to investigate whether SST can reduce liver injury and alleviate the process of LF by inhibiting the ERS.Methods Forty WT mice were randomly divided into control, model, low-dose SST-intervened and large-dose SST-intervened group, with 10 in each. Except the mice in control, the mice in other groups were injected with 25% CCl₄ and oil mixture intraperitoneally to establish the model of liver injury and the mice in SST-intervened groups were given large or low doses of SST subcutaneously, respectively. Serum ALT and AST were detected, the liver tissues were obtained for pathological examination, and the protein expression of Bcl-2, Bax, Casp-9, BiP and CHOP in liver tissues were detected by Western blot.Results The histological activity index (HAI) score in model group was (12.2±2.7), significantly higher than [(1.8±0.8), P＜0.01] in the control, and the hepatic fibrosis score was (5.4±0.5), significantly higher than [(0.1±0.3),P＜0.01] in control; serum AST and ALT in the model were (194.7±35.2)U/L and (121.8±26.6)U/L], both significantly higher than [(53.8±21.7)U/L and (35.3±12.9)U/L, respectively,P＜0.01] in the control; the HAI scores in low-dose and large-dose SST-intervened groups were (7.7±2.1) and (6.9±2.0), and the hepatic fibrosis scores were (4.3±1.0) and (3.9±0.9), significantly decreased compared to those in the model (P＜0.05); the expression of Bax, Casp-9, BiP and CHOP in hepatic tissues in the model intensified greatly compared to in the control ([P＜0.01), while the hepatic expression of Bax, Casp-9, BiP and CHOP in SST-intervened groups weaken obviously compared to in the model (F=26.36, F=14.81, F=25.11 and F=30.31,P＜0.05).Conclusion SST could alleviate liver inflammation and LF, the mechanism by which might be related to the inhibition of ERS.

Key words: Liver fibrosis, Somatostatin, Endoplasmic reticulum stress, Histological activity index, Mice

Du Qingguo, Lu Jianwen, Wang Jianhua, et al. Somatostatin alleviates liver injury in mice with liver fibrosis by inhibiting endoplasmic reticulum stress[J]. Journal of Practical Hepatology, 2021, 24(2): 172-175.

References

[1] Hernandez-Gea V, Friedman SL. Pathogenesis of liver fibrosis. Annu Rev Pathol, 2011, 6:425-456.
[2] 陈宵瑜, 杨长青. 肝纤维化发生机制研究新进展. 实用肝脏病杂志, 2016, 19(1):121-124.
[3] Schaffner F, Klion FM. Chronic hepatitis. Annu Rev Med, 1968, 19:25-38.
[4] Bravo R, Parra V, Gatica D, et al. Endoplasmic reticulum and the unfolded protein response: dynamics and metabolic integration. Int Rev Cell Mol Biol, 2013, 301:215-290.
[5] Iurlaro R, Munoz-Pinedo C. Cell death induced by endoplasmic reticulum stress. FEBS J, 2016, 283(14):2640-2652.
[6] Demirtas L, Guclu A, Erdur FM, et al. Apoptosis, autophagy & endoplasmic reticulum stress in diabetes mellitus. Indian J Med Res, 2016, 144(4):515-524.
[7] 潘高峰, 傅茂英, 郜玉峰. 内质网应激与肝纤维化关系研究进展. 实用肝脏病杂志, 2018, 21(6): 987-990.
[8] Yabuki K, Maekawa T, Satoh K, et al. Extensive hemorrhagic erosive gastritis associated with acute pancreatitis successfully treated with a somatostatin analog. J Gastroenterol, 2002, 37(9):737-741.
[9] Du Z, Zhou Y, Lu X, et al. Octreotide prevents liver failure through upregulating 5'-methylthioadenosine in extended hepatectomized rats. Liver Int, 2016, 36(2):212-222.
[10] Tsuchida T, Lee YA, Fujiwara N, et al. A simple diet- and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer. J Hepatol, 2018, 69(2):385-395.
[11] Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol, 1995, 22(6): 696-699.
[12] Andruszkow J, Hartleben B, Schlué J, et al. Staging of liver fibrosis in biliary atresia : comparison of chevallier and ishak score as well as automated evaluation. Pathology, 2019, 40(1): 85-92.
[13] Zhang CY, Yuan WG, He P, et al. Liver fibrosis and hepatic stellate cells: etiology, pathological hallmarks and therapeutic targets. World J Gastroenterol, 2016, 22(48):10512-10522.
[14] El Taghdouini A, van Grunsven LA. Epigenetic regulation of hepatic stellate cell activation and liver fibrosis. Expert Rev Gastroenterol Hepatol, 2016, 10(12): 1397-1408.
[15] Campana L, Iredale JP. Regression of liver fibrosis. Semin Liver Dis, 2017, 37(1): 1-10.
[16] Osawa Y, Hoshi M, Yasuda I, et al. Tumor necrosis factor-α promotes cholestasis-induced liver fibrosis in the mouse through tissue inhibitor of metalloproteinase-1 production in hepatic stellate cells. PloS One, 2013, 8(6): e65251.
[17] Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol, 2017, 14(7):397-411.
[18] Malhi H, Kaufman RJ. Endoplasmic reticulum stress in liver disease. J Hepatol, 2011, 54(4): 795-809.
[19] Delbrel E, Soumare A, Naguez A, et al. HIF-1α triggers ERS and CHOP-mediated apoptosis in alveolar epithelial cells, a key event in pulmonary fibrosis. Sci Rep, 2018, 8(1): 17939.
[20] 甘厦, 方念, 黄神安, 等. 内镜套扎术联合生长抑素治疗肝硬化并发食管静脉曲张出血患者临床效果和安全性分析. 实用肝脏病杂志, 2019, 22(2):236-239.

Somatostatin alleviates liver injury in mice with liver fibrosis by inhibiting endoplasmic reticulum stress

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