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[硫化氢对1型糖尿病大鼠肾脏诱导型一氧化氮合酶的影响]

[Effect of hydrogen sulfide on inducible nitric oxide synthase in kidneys of Type 1 diabetic rats].

作者信息

Yang Rui, Jia Qiang, Ma Shanfeng, Cui Shujun, Liu Xiaofen, Wang Yuanyuan, Gao Qin

机构信息

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

Department of Bioscience, Bengbu Medical College, Bengbu Anhui 233030, China.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2017 Apr 28;42(4):389-394. doi: 10.11817/j.issn.1672-7347.2017.04.004.

DOI:10.11817/j.issn.1672-7347.2017.04.004
PMID:28490695
Abstract

To investigate effects of hydrogen sulfide (H2S) on inducible nitric oxide synthase (iNOS) in kidneys of Type 1 diabetic rats.
 Methods: Thirty-two male SD rats were randomly divided into four groups: A normal control (NC) group, a diabetes mellitus (DM) group, a NaHS (NaHS+DM) group, and a NaHS control (NaHS) group (n=8 per group). Type 1 diabetes was induced by a single intraperitoneal injection of streptozotocin (55 mg/kg). After successful establishment of models, the rats in NaHS+DM and NaHS groups were injected with NaHS solution (56 μmol/kg) intraperitoneally. Eight weeks later, the activities of total nitric oxide synthase (T-NOS) and iNOS, as well as the level of nitric oxide (NO) were detected in serum and renal tissues, respectively. The activity of glutathione peroxidase (GSH-Px) was determined in renal tissues. The ultrastructures of renal tissues were observed by transmission electron microscope. The protein expression of iNOS in renal tissues was detected by Western blot.
 Results: Compared with the NC group, there was no significant difference in the various indexes in the NaHS group (P>0.05). However, in the DM group, the activities of T-NOS and iNOS, and the level of NO were all increased significantly in serum and renal tissues, while the activity of GSH-Px was decreased in renal tissues. Under the electronic microscope, the thickening of the glomerular capillary basement membrane, the proliferation of mesangial matrix, and the foot fusion were observed. The protein expression of iNOS was increased obviously in renal tissues in the DM group (P<0.01). Compared with the DM group, the activities of T-NOS and iNOS and the level of NO were all decreased in serum and renal tissues, while the activity of GSH-Px was increased in renal tissues in the NaHS+DM group (P<0.01). The renal ultrastructural damages were ameliorated obviously. The protein expression of iNOS was decreased significantly (P<0.01).
 Conclusion: H2S exerts a protective effect on kidney injury in type 1 diabetic rats. The mechanism might be related to inhibition of iNOS activity and protein expression, in turn leading to reduction of NO content in renal tissues.

摘要

探讨硫化氢(H₂S)对1型糖尿病大鼠肾脏诱导型一氧化氮合酶(iNOS)的影响。方法:将32只雄性SD大鼠随机分为四组:正常对照组(NC组)、糖尿病组(DM组)、硫氢化钠组(NaHS + DM组)和硫氢化钠对照组(NaHS组)(每组n = 8)。通过单次腹腔注射链脲佐菌素(55 mg/kg)诱导1型糖尿病。成功建立模型后,NaHS + DM组和NaHS组大鼠腹腔注射硫氢化钠溶液(56 μmol/kg)。8周后,分别检测血清和肾组织中总一氧化氮合酶(T - NOS)和iNOS的活性以及一氧化氮(NO)水平。测定肾组织中谷胱甘肽过氧化物酶(GSH - Px)的活性。通过透射电子显微镜观察肾组织的超微结构。采用蛋白质免疫印迹法检测肾组织中iNOS的蛋白表达。结果:与NC组相比,NaHS组各项指标差异无统计学意义(P > 0.05)。然而,DM组血清和肾组织中T - NOS和iNOS的活性以及NO水平均显著升高,而肾组织中GSH - Px的活性降低。电镜下可见肾小球毛细血管基底膜增厚、系膜基质增生和足突融合。DM组肾组织中iNOS的蛋白表达明显增加(P < 0.01)。与DM组相比,NaHS + DM组血清和肾组织中T - NOS和iNOS的活性以及NO水平均降低,而肾组织中GSH - Px的活性升高(P < 0.01)。肾超微结构损伤明显改善。iNOS的蛋白表达显著降低(P < 0.01)。结论:H₂S对1型糖尿病大鼠肾损伤具有保护作用。其机制可能与抑制iNOS活性和蛋白表达有关,进而导致肾组织中NO含量降低。

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