Jia Qiang, Wang Lei, Wang Qi-Yi, Liu Xiao-Fen, Ma Shan-Feng, Yang Rui
Department of Physiology, Bengbu Medical College, Bengbu 233030, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2018 Jun 8;34(6):572-576. doi: 10.12047/j.cjap.5734.2018.128.
To investigate the effects of hydrogen sulfide (HS) on renal fibrosis in diabetic rats and explore its mechanism.
Male Sprague-Dawley rats were randomly divided into normal control (NC) group, a diabetic control (DC) group, diabetes mellitus (DM)+sodium hydrosulfide (NaHS) group and DM+DL-propargylglycine (PAG) group, with 8 rats in each group.Type 1 diabetes was induced in the respective groups by a single intraperitoneal (i.p.) injection of streptozotocin.From the fifth week, rats in the DM+NaHS and DM+PAG groups were injected (i.p.) with 56 μmol/kg NaHS and 40 mg/kg PAG once a day, respectively.After treatment for 4 weeks, the levels of fasting blood glucose (FBG), blood urea nitrogen (BUN) and serum creatinine (SCr) were detected.The deposition of renal collagen fibers was observed by Masson staining, and collagen volume fraction (CVF) was calculated.The ultrastructural change of renal tissue was observed by transmission electron microscopy.The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and hydroxyproline (Hyp) in renal tissues were detected using the kits.The expression levels of TGF-β1, Smad3, phosphorylated (p)-Smad3 and collagen-IV (col-IV) in renal tissues were detected using Western blot.
Compared with the NC group, the levels of FBG, BUN, SCr, CVF, IL-1β, IL-6, TNF-α and Hyp were increased; the deposition of renal collagen fibers and the ultrastructural damage were aggravated; the levels of TGF-β1, Smad3, p-Smad3, p-Smad3/Smad3 and col-IV were increased in the DC group.Compared with the DC group, excluding FBG, the aforementioned indices were improved in the DM+NaHS group; the aforementioned indices were further aggravated in the DM+PAG group.
HS attenuated renal fibrosis in diabetic rats, and the mechanism might be associated with the reduction of the release of proinflammatory cytokines, downregulation of the TGF-β1/Smad3 pathway, and inhibition of excessive accumulation of col-IV.
探讨硫化氢（HS）对糖尿病大鼠肾纤维化的影响并探究其机制。
将雄性Sprague-Dawley大鼠随机分为正常对照组（NC组）、糖尿病对照组（DC组）、糖尿病（DM）+硫氢化钠（NaHS）组和DM+DL-炔丙基甘氨酸（PAG）组，每组8只。通过单次腹腔注射链脲佐菌素在各组诱导1型糖尿病。从第5周起，DM+NaHS组和DM+PAG组大鼠分别每天腹腔注射56 μmol/kg NaHS和40 mg/kg PAG。治疗4周后，检测空腹血糖（FBG）、血尿素氮（BUN）和血清肌酐（SCr）水平。采用Masson染色观察肾胶原纤维沉积情况，并计算胶原容积分数（CVF）。通过透射电子显微镜观察肾组织超微结构变化。使用试剂盒检测肾组织中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和羟脯氨酸（Hyp）水平。采用蛋白质免疫印迹法检测肾组织中转化生长因子-β1（TGF-β1）、Smad3、磷酸化（p）-Smad3和Ⅳ型胶原（col-IV）的表达水平。
与NC组相比，DC组FBG、BUN、SCr、CVF、IL-1β、IL-6、TNF-α和Hyp水平升高；肾胶原纤维沉积及超微结构损伤加重；TGF-β1、Smad3、p-Smad3、p-Smad3/Smad3和col-IV水平升高。与DC组相比，DM+NaHS组除FBG外，上述指标均得到改善；DM+PAG组上述指标进一步加重。
HS减轻糖尿病大鼠肾纤维化，其机制可能与减少促炎细胞因子释放、下调TGF-β1/Smad3通路以及抑制col-IV过度蓄积有关。
