缬沙坦对大鼠急性肝衰竭的保护作用及其机制研究

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Abstract Objective To investigate the protective effect and mechanism of Valsartan on acute liver failure in rats. Methods A total of sixty healthy male SD rats were divided into normal control group, liver failure group, and Valsartan group by random number table method, with 20 rats in each group. Normal control group was intraperitoneally injected with normal saline, liver failure group was intraperitoneally injected with D-galactosamine (D-GalN) / lipopolysaccharide (LPS) for modeling; Valsartan group was intraperitoneally injected with Valsartan (25 mg/kg) 30 min before modeling. The survival of rats in each group was observed. The levels of angiotensinⅡ (AngⅡ) and angiotensin 1-7 (Ang 1-7), and the radio of AngⅡ/Ang 1-7 in serum and liver tissues, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in serum of rats were detected ten hours after model building. The level of inflammation andnecrosis in liver tissues was observed. The expression levels of glucose regulatory protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in liver tissues were detected. Results The survival rate in Valsartan group was higher than that in liver failure group, and the difference was highly statistically significant (P ＜ 0.01). The levels of AngⅡ and the radio of AngⅡ/Ang 1-7 in serum and liver tissues in Valsartan group were lower than those in liver failure group, and Ang 1-7 in Valsartan group were higher than that in liver failure group, with high statistical significance (all P ＜ 0.01). Serum levels of ALT, AST, TNF-α and IL-6 in Valsartan group were lower than those in liver failure group, and the differences were highly statistically significant (all P ＜ 0.01). In the liver failure group, the structure of liver lobules of part of liver tissues was disordered and the degeneration and necrosis of liver cells were serious. The degeneration and necrosis of liver cells in Valsartan group was less than that in liver failure group. The expression levels of GRP78 and CHOP in liver tissues of Valsartan group were lower than those of liver failure group, and the differences were highly statistically significant (all P ＜ 0.01). Conclusion Valsartan can significantly reduce liver inflammation and liver cell apoptosis in the process of acute liver failure by blocking renin-angiotensin system, and its protective effect may be related to the inhibition of endoplasmic reticulum stress.

Key words： Acute liver failure Renin-angiotensin system Endoplasmic reticulum stress AngiotensinⅡ

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	LI Jianzhou1 LIU Xiaojing1 YE Feng1 LI Xiaoqing2

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LI Jianzhou1 LIU Xiaojing1 YE Feng1 LI Xiaoqing2. Study on the protective effect and mechanism of Valsartan on acute liver failure in rats[J]. 中国医药导报, 2021, 18(16): 4-8,29.

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https://www.yiyaodaobao.com.cn/EN/ OR https://www.yiyaodaobao.com.cn/EN/Y2021/V18/I16/4

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