硫化氢对糖尿病大鼠肾脏纤维化的影响及其机制

doi:10.12047/j.cjap.5734.2018.128

中国应用生理学杂志 ›› 2018, Vol. 34 ›› Issue (6): 572-576.doi: 10.12047/j.cjap.5734.2018.128

• 研究论文 • 上一篇

硫化氢对糖尿病大鼠肾脏纤维化的影响及其机制

贾强, 王蕾, 王其一, 刘小粉, 马善峰, 杨锐

蚌埠医学院生理学教研室, 安徽蚌埠 233030

收稿日期:2018-08-09 修回日期:2018-11-06 出版日期:2018-11-28 发布日期:2019-03-09
通讯作者: 杨锐 E-mail:xzxyr@sina.com
基金资助:
安徽省高校自然科学研究重点项目（KJ2017A216，KJ2018A0994）；蚌埠医学院科研项目（BYKY1621ZD，BYKF1706）

Effects of hydrogen sulfide on renal fibrosis in diabetic rats and its mechanism

JIA Qiang, WANG Lei, WANG Qi-yi, LIU Xiao-fen, MA Shan-feng, YANG Rui

Department of Physiology, Bengbu Medical College, Bengbu 233030, China

Received:2018-08-09 Revised:2018-11-06 Online:2018-11-28 Published:2019-03-09
Supported by:
安徽省高校自然科学研究重点项目（KJ2017A216，KJ2018A0994）；蚌埠医学院科研项目（BYKY1621ZD，BYKF1706）

摘要/Abstract

摘要： 目的：观察硫化氢（H₂S）对糖尿病大鼠肾脏组织纤维化的影响并探讨其作用机制。方法：雄性SD大鼠随机分为正常对照（NC）组、糖尿病对照（DC）组、糖尿病+硫氢化钠（DM+NaHS）组和糖尿病+炔丙基甘氨酸（DM+PAG）组，每组8只。采用一次性腹腔注射链脲佐菌素的方法制备1型糖尿病大鼠模型。造模成功4周后，DM+NaHS组和DM+PAG组大鼠每天分别腹腔注射56 μmol/kg NaHS和40 mg/kg PAG溶液。处理4周后，测定各组大鼠空腹血糖（FBG）、尿素氮（BUN）和肌酐（SCr）水平；Masson染色观察肾脏组织胶原纤维变化，计算胶原容积分数（CVF）；透射电镜观察肾脏超微结构；利用试剂盒检测肾组织白细胞介素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；Western blot测肾组织TGF-β1、Smad3、磷酸化Smad3（p-Smad3）和IV型胶原（col-IV）的蛋白表达水平。结果：与NC组比较，DC组FBG、BUN、SCr、CVF、IL-1β、IL-6、TNF-α和Hyp均明显增高，肾脏胶原纤维沉积、超微结构损伤明显加重，TGF-β1、Smad3、p-Smad3、p-Smad3/Smad3和col-IV表达均明显增加。与DC组比较，除FBG外，DM+NaHS组中上述指标均明显改善；而DM+PAG组中上述指标损伤均进一步加重。结论：H₂S可以减轻糖尿病大鼠肾脏纤维化，其机制可能与减少促炎因子释放，下调TGF-β1/Smad3通路，抑制肾脏col-IV过量生成相关。

关键词: 硫化氢, 糖尿病, 肾脏, 纤维化, 转化生长因子β1/Smad3通路, 大鼠

Abstract: Objective: To investigate the effects of hydrogen sulfide (H₂S) on renal fibrosis in diabetic rats and explore its mechanism.Methods: 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.Results: 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.Conclusion: H₂S 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.

Key words: hydrogen sulfide, diabetes mellitus, kidney, fibrosis, transforming growth factor-β1/Smad3 pathway, rat

贾强, 王蕾, 王其一, 刘小粉, 马善峰, 杨锐. 硫化氢对糖尿病大鼠肾脏纤维化的影响及其机制[J]. 中国应用生理学杂志, 2018, 34(6): 572-576.

JIA Qiang, WANG Lei, WANG Qi-yi, LIU Xiao-fen, MA Shan-feng, YANG Rui. Effects of hydrogen sulfide on renal fibrosis in diabetic rats and its mechanism[J]. CJAP, 2018, 34(6): 572-576.

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硫化氢对糖尿病大鼠肾脏纤维化的影响及其机制

Effects of hydrogen sulfide on renal fibrosis in diabetic rats and its mechanism

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