目的:观察硫化氢(H2S)对1型糖尿病大鼠肾脏的保护作用及其机制。方法:32只雄性SD大鼠随机分为4组:正常对照(NC)组、糖尿病(DM)组、糖尿病治疗(NaHS+DM)组和NaHS对照(NaHS)组(n=8)。DM组和NaHS+DM组大鼠采用链脲佐菌素(STZ)55 mg/kg腹腔注射诱导1型糖尿病模型。造模成功后,NaHS+DM组和NaHS组采用腹腔注射NaHS溶液56μmol/kg干预治疗。8周后,测定大鼠24 h尿蛋白含量、肾重指数、空腹血糖、尿素氮、肌酐等指标;HE染色观察肾脏组织形态学变化;测定肾脏组织脂质过氧化物丙二醛(MDA)含量、超氧化物歧化酶(SOD)和Caspase-3的活性;Western blot检测肾脏组织Bcl-2和Bax蛋白表达。结果:与NC组相比,NaHS组各项指标均无显著差异,DM组,24 h尿蛋白含量、肾重指数、空腹血糖、尿素氮和肌酐水平均明显升高;HE染色结果显示肾小球基底膜增厚、系膜基质增多;MDA含量、Caspase-3活性和Bax蛋白表达明显增高;SOD活性和Bcl-2蛋白表达显著降低。与DM组相比,NaHS+DM组肾功能损伤明显减轻,肾脏组织形态学变化明显改善,MDA含量、Caspase-3活性和Bax蛋白表达明显下降,SOD活性和Bcl-2蛋白表达显著增高。结论:H_2S对1型糖尿病大鼠肾脏具有保护作用,其机制可能与抑制氧化应激和细胞凋亡有关。
Objective: To explore the protective effects of hydrogen sulfide (H2S) on kidneys of type 1 diabetic rats and its underlying mechanism. Methods: Thirty-two male SD rats were randomly divided into four groups:normal control (NC) group, diabetes mellitus (DM) group, DM treatment (NariS + DM) group and NariS control (NariS) group. The rats from DM group and NariS + DM group were injected in- traperitoneally with Streptozotecin 55 mg/kg to induce type 1 diabetes mellitus ( n = 8). After modeling, rats in NariS + DM group and NariS group were intraperitoneally injected with NariS solution at the dosage of 56 μmol/kg. After 8 weeks, urinary protein content was detected in urine samples collected for 24 h. and the ratio of kidney weight/body weight (renal index) was determined in isolated kidneys. Besides, the levels of fasting blood glucose (FBG), blood urea nitrogen (BUN) and serum creatinine (Scr) were measured biechemically. The morphological changes of renal tissue were observed by HE staining. The content of malondialdehyde (MDA), the activities of superoxide dismutase (SOD) and Caspase-3 in renal tissue were detennined by spectrophotometry. The protein expression levels of Bcl-2 and Bax in renal tissue were detected using Western blot. Results: There was no significant difference in the respective measured indexes in rats between NC group and NariS group. However, in DM group, the levels of24 h urinary protein, FBG, BUN, Scr and renal index were increased significantly; HE staining showed that the basement membrane was thickened and the amount of glomerular mesangial matrix was increased; MDA content, Caspase-3 activity and Bax expression levels were increased, while SOD activity and Bcl-2 expression were decreased. Compared with those in DM group, the morphological changes of renal tissue and its function were improved; MDA content, Caspase-3 activity and Bax expression were decreased significantly, while SOD activity and Bcl-2 expression were increa