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中国应用生理学杂志 ›› 2020, Vol. 36 ›› Issue (4): 318-320.doi: 10.12047/j.cjap.5965.2020.068

• 研究论文 • 上一篇    下一篇

外源性H2S对糖尿病小鼠肝纤维化的作用及其机制*

席雨鑫, 温馨, 矫立杰, 魏亚新, 常贵全, 武韧, 孙凤起, 郝静辉, 李鸿珠   

  1. 哈尔滨医科大学基础医学院病理生理学教研室, 黑龙江 哈尔滨 150086
  • 收稿日期:2019-11-01 修回日期:2020-06-16 发布日期:2020-11-09
  • 通讯作者: Tel: 0451-86674548; E-mail: hongzhuli61@163.com
  • 基金资助:
    *国家自然科学基金(81770486)

Effects of exogenous H2S on hepatic fibrosis in diabetic mice and its mechanism

XI Yu-xin, WEN Xin, JIAO Li-jie, WEI Ya-xin, CHANG Gui-quan, WU Ren, SUN Feng-qi, HAO Jing-hui, LI Hong-zhu   

  1. Departmentof Pathophysiology, Harbin Medical University, Harbin 150086, China
  • Received:2019-11-01 Revised:2020-06-16 Published:2020-11-09

摘要: 目的: 探讨外源性硫化氢(H2S)对糖尿病小鼠肝纤维化作用及其相关机制。方法: 将 C57 雄性体重为(22±2)g 24只小鼠随机分为3组(n=8):①正常对照组(Control):小鼠腹腔注射生理盐水,注射时间同实验组;②糖尿病模型组(HG):按体重(150 mg/kg)一次性腹腔注射链脲佐菌素(STZ)诱导小鼠建立糖尿病模型;③NaHS 处理组(HG + NaHS):方法同组别②,只是糖尿病模型建立后,腹腔注射NaHS(100 μmol/L·kg·d),每天一次,连续12周。HE染色检测肝细胞损伤;Masson染色检测肝纤维化;Western blot检测相关蛋白胱硫醚-β-合成酶(CBS,内源性H2S产生的关键酶)、胶原I (Col-I)、胶原III (Col-III)和基质金属蛋白酶-9(MMP-9)的表达。结果: 与对照组比较,糖尿病模型组肝细胞损伤及肝纤维化均显著加重,CBS 蛋白表达显著减少(P<0.01),Col-I、Col-III和MMP-9蛋白表达均显著增加(P<0.01)。与糖尿病模型组比较,NaHS处理组肝细胞损伤及肝纤维化均显著减轻、CBS 蛋白表达显著增加、Col-I、Col-III和MMP-9蛋白表达均减少(P<0.01)。结论: 外源性H2S可抑制糖尿病小鼠肝纤维化,其机制与降低胶原含量和基质金属蛋白酶-9的表达相关。

关键词: 硫化氢, 肝纤维化, 糖尿病, 小鼠

Abstract: Objective: To investigate the effects of exogenous hydrogen sulfide (H2S) on the hepatic fibrosis in diabetic mice and its mechanism. Methods: Twenty-four C57 male mice (weight 22±2 g) were randomly divided into three groups (n=8): ① Normal control group (Control): Mice were intraperitoneally injected equal amount of normal saline, the injection time was the same as that of the experimental groups; ② Diabetes model groups (HG): Streptozotocin (STZ) was injected intraperitoneally once according to body weight (150 mg/kg) to establish diabetes model; ③ NaHS treatment groups (HG + NaHS): Mice were intraperitoneally injected with NaHS (100 μmol/L·kg·d) once a day for 12 consecutive weeks. The hepatocyte injury was detected by HE staining; the hepatic fibrosis was observed through Masson staining; the protein expressions of cystathionine - β - synthetase (CBS), collagen-I (CoL-I), collagen-III (CoL-III) and matrix metalloproteinase-9 (MMP-9) were detected by Western blot. Results: Compared with the control group, the damage and fibrosis of hepatocyte were significantly aggravated, the expression of CBS proteins was decreased (P<0.01), and the expression levels of CoL-I, CoL-III and MMP-9 proteins were increased (P<0.01) in the diabetic model group. Compared with the diabetic model group, the damage and fibrosis of hepatocyte were significantly lightened, the expression of CBS proteins was obviously increased (P<0.01), and the expression levels of CoL-I, CoL-III and MMP-9 proteins were markedly decreased (P< 0.01). Conclusion: H2S inhibits the hepatic fibrosis in diabetic mice, and its mechanism is related to the decrease of collagen and matrix metalloproteinase-9.

Key words: hydrogen sulfide, hepatic fibrosis, diabetes, mice

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