【摘要】 目的:探讨外源性硫化氢（H2S）在小鼠阻塞性肾损伤中的保护作用及可能机制。方法:将8周龄的雄性C57BL/6小鼠随机分为假手术组、手术组和H2S组,每组5只,单侧输尿管结扎（UUO）构建肾阻塞模型,H₂S组小鼠腹腔注射H₂S供体硫氢化钠（Na HS）,手术组和假手术组小鼠注射等体积的生理盐水,每天1次。7 d后处死小鼠,取出肾脏,提取RNA行RT-PCR检测3组小鼠肾脏内源性H₂S催化酶mRNA表达的差异;组织HE染色观察3组小鼠肾脏的组织结构的变化;Masson染色检测3组小鼠肾脏纤维化的差异;检测血浆胱抑素C含量来反映肾小球滤过能力;Western blot检测LC3、beclin-1和纤连蛋白（FN）蛋白表达的变化。结果:与假手术组相比,手术组小鼠肾脏中胱硫醚β-合成酶（CBS）、胱硫醚γ-裂解酶（CSE）和3-巯基丙酮酸硫转移酶（3-MST）的mRNA表达显著降低,胶原纤维显著增多,而H₂S组小鼠肾组织胶原纤维又比模型组显著减少。与假手术组相比,手术组小鼠肾脏中FN的蛋白表达显著升高,而H₂S组小鼠的FN表达量比手术组小鼠显著降低;与假手术组相比,手术组和H₂S组小鼠肾组织细胞中LC3-II和beclin-1蛋白表达均显著增高,而H₂S组小鼠肾组织细胞中LC3-II和beclin-1蛋白表达又显著高于手术组。结论:外源性H₂S可能通过上调细胞自噬而减轻UUO小鼠的肾纤维化。更多还原

【Abstract】 AIM: To investigate the protective effect of exogenous hydrogen sulfide（ H2 S） on obstructive renal injury in mice,and to explore the possible potential mechanisms involved in this animal model. METHODS: Male C57 BL/6 mice（ 8 weeks old） were randomly divided into sham group,operation group and H₂ S group,with 5 rats in each group. The model of obstructive renal injury was induced by unilateral ureteral obstruction（ UUO）. The mice in H₂ S group were intraperitoneally injected with Na HS daily,while the mice in sham group and operation group were administered with the same volume of saline intraperitoneally. After 7 d,the mice were executed and the renal tissues were taken out for experiments. RNA was extracted to detect the mRNA expression of H₂ S catalytic enzymes in the mice of 3 groups. HE staining was performed to observe the structural changes of renal tissues in the mice. Renal fibrosis in the mice of 3 groups was evaluated by Masson staining. The content of cystatin C in the plasma was detected to reflect glomerular filtration ability.The protein expression of LC3,beclin-1 and fibronectin（ FN） in the mice of 3 groups was determined by Western blot.RESULTS: Compared with sham group,the mRNA expression of cystathionine β-synthase（ CBS）,cystathionine γ-lyase（ CSE） and 3-mercaptopyruvate sulfurtransferase（ 3-MST） in operation group decreased significantly. The collagen fiber content in operation group was increased significantly,while collagen fiber content in H2 S group was decreased significantly as compared with operation group. Compared with sham group,the protein expression of FN in operation group was increased significantly,while the protein expression of FN in H₂ S group was decreased significantly as compared with operation group.Compared with sham group,the protein expression of LC-II and beclin-1 in operation group was increased significantly,while the protein expression of LC-II and beclin-1 in H2 S group was increased significantly as compared with the operation group.CONCLUSION: Exogenous H2 S possibly mitigates renal fibrosis in UUO mice by up-regulating autophagy.更多还原