| 肝星状细胞核糖体蛋白S5（RPS5）特异性敲减对肝纤维化的影响 |
| 投稿时间：2022-09-04 修订日期：2023-01-30 点此下载全文 |
| 引用本文：汤玉珍,张俊平.肝星状细胞核糖体蛋白S5（RPS5）特异性敲减对肝纤维化的影响[J].药学实践杂志,2023,41(4):227~233 |
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| 基金项目:福建中医药大学高层次人才科研启动资金项目（X2019005) |
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| 中文摘要:目的 观察特异性敲减肝星状细胞（HSC）内核糖体蛋白S5（RPS5）对大鼠肝纤维化的影响。方法 构建胶质纤维酸性蛋白（GFAP）启动子驱动的RPS5 shRNA腺病毒，分别用AdGFa2-shRPS5及其对照AdGFa2 shNC转染大鼠原代HSC和肝细胞，通过蛋白印迹法和实时PCR测定RPS5、α-SMA和I型胶原表达情况；采用二甲基亚硝胺（DMN）和胆管结扎术（BDL）的方法建立大鼠肝纤维化模型，尾静脉注射腺病毒特异性敲减肝内HSC的RPS5水平。肝组织切片HE染色分析病理改变情况；羟脯氨酸含量测定、切片天狼星红和 Masson染色评价胶原沉积情况；免疫组织化学染色检测α-SMA和RPS5的表达情况。结果 AdGFa2-shRPS5能够特异性敲减HSC中的RPS5表达水平，增加α-SMA和I型胶原在体外表达。体内研究结果表明，在两种慢性肝损伤动物模型中，特异性敲减HSC中RPS5表达水平能够促进HSC活化，增加细胞外基质的沉积，促进肝纤维化。结论 RPS5对HSC激活和肝纤维化发生至关重要，可能是治疗肝纤维化的潜在靶点。 |
| 中文关键词:核糖体蛋白S5 肝星状细胞 胶质纤维酸性蛋白 肝星状细胞活化 肝纤维化 |
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| Effects of specific knockdown of ribosomal protein S5 in hepatic stellate cells on liver fibrosis |
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| Abstract:Objective To observe the effect of specific knockdown of hepatic stellate cells (HSC) ribosomal protein S5 (RPS5) on liver fibrosis in rats. Methods The glial fibrillary acidic protein (GFAP) promoter-driven RPS5 shRNA adenovirus was established, and AdGFa2-shRPS5 and its control AdGFa2 shNC were used to transfect primary rat HSCs and hepatocytes, respectively. RPS5 was determined by Western-blot and Real Time PCR, α-SMA and type I collagen expression; the rat liver fibrosis model was established by dimethyl nitrosamine (DMN) and bile duct ligation (BDL), and intrahepatic HSC was specifically knocked down by tail vein injection of adenovirus of RPS5 levels. The pathological changes of liver tissue sections were analyzed by HE staining; the content of hydroxyproline, sections of Sirius red and Masson staining were used to evaluate collagen deposition; immunohistochemical staining was used to detect the expression of α-SMA and RPS5. Results AdGFa2-shRPS5 specifically knocked down the expression level of RPS5 in HSC and increased the expression of α-SMA and type I collagen in vitro. The in vivo results showed that in two animal models of chronic liver injury, specific knockdown of RPS5 expression in HSCs promoted HSC activation, increased the deposition of extracellular matrix, and promoted liver fibrosis. Conclusion RPS5 is essential for HSC activation and liver fibrosis, which could be a potential target for the treatment of liver fibrosis. |
| keywords:ribosomal protein S5 hepatic stellate cells glial fibrillary acidic protein HSC activation hepatic fibrosis |
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