Hydrogen sulfide treatment protects against renal ischemia-reperfusion injury via induction of heat shock proteins in rats
Hydrogen sulfide treatment protects against renal ischemia-reperfusion injury via induction of heat shock proteins in rats
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DOI：
10.22038/ijbms.2018.29706.7170
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发表时间：
2019-01-01
影响因子：
2.2
通讯作者：
Xiao, Cheng-cheng
中科院分区：
文献类型：
--
作者：
Du, Yang;Liu, Xiu-heng;Xiao, Cheng-cheng
目标：硫化氢 (H2S) 减轻不同器官的缺血再灌注损伤 (IRI)。然而，其在肾 IRI 中的作用机制仍不清楚。本研究调查了 H2S 通过诱导热休克蛋白 (HSP) 减弱肾脏 IRI 的假设。材料和方法：成年 Wistar 大鼠单侧肾缺血 45 分钟，然后再灌注 6 小时。一组大鼠在不进行治疗的情况下进行 I/R，一组在 I/R 前给予 150 μmol/l 硫氢化钠 (NaHS)，一组在 I/R 前腹腔注射 100 mg/kg 槲皮素（一种 HSP 抑制剂），另一组在 I/R 前接受槲皮素并在 I/R 后接受 NaHS 治疗。另外两组进行假手术，其中一组在假手术后接受 150 μmol/l NaHS，而另一组则不接受任何治疗。比较肾功能和组织学变化，并检测氧化应激、细胞凋亡和炎症的相关指标。结果：IRI增加血清肌酐和血尿素氮浓度，通过升高丙二醛水平促进脂质过氧化，抑制超氧化物歧化酶活性，通过诱导NF-κB、IL-2和TLR-4表达刺激炎症，并增加肾细胞凋亡。 IRI 后 HSP 70、血红素加氧酶 1 (HO-1) 和 HSP 27 水平升高，而 H2S 治疗后则逆转。 H2S 减弱了 IRI 后观察到的病理学、脂质过氧化、炎症和细胞凋亡的变化。槲皮素的施用逆转了H2S的所有保护作用。结论：本研究表明H2S保护肾组织免受IRI诱导的脂质过氧化、炎症和细胞凋亡，这可能归因于HSP 70、HO-1和HSP 27的上调。
Objective(s): Hydrogen sulfide (H2S) attenuates ischemia-reperfusion injury (IRI) in different organs. However, its mechanism of action in renal IRI remains unclear. The present study investigated the hypothesis that H2S attenuates renal IRI via the induction of heat shock proteins (HSPs).Materials and Methods: Adult Wistar rats were subjected to unilateral renal ischemia for 45 min followed by reperfusion for 6 hr. One group of rats underwent I/R without treatment, one group was administered 150 mu mol/l sodium hydrosulfide (NaHS) prior to I/R, one group was injected with 100 mg/kg quercetin (an HSP inhibitor) intraperitoneally prior to I/R, and another group received quercetin prior to I/R and treatment with NaHS following I/R. Two other groups underwent a sham operation and one of them received 150 mu mol/l NaHS following the sham operation whereas the other received no treatment. Renal function and histological changes were compared and relevant indices of oxidative stress, apoptosis, and inflammation were examined.Results: IRI increased serum creatinine and blood urea nitrogen concentrations, promoted lipid peroxidation by elevating malondialdehyde levels, suppressed superoxide dismutase activity, stimulated inflammation by inducing NF-kappa B, IL-2, and TLR-4 expression, and increased renal apoptosis. Levels of HSP 70, heme-oxygenase-1 (HO-1) and HSP 27 were increased following IRI and reversed following H2S treatment. H2S attenuated changes observed in pathology, lipid peroxidation, inflammation, and apoptosis following IRI. The administration of quercetin reversed all protective effects of H2S.Conclusion: The present study indicated that H2S protected renal tissue against IRI induced lipid peroxidation, inflammation, and apoptosis, which may be attributed to the upregulation of HSP 70, HO-1, and HSP 27.