Melatonin prevents sepsis-induced renal injury via the PINK1/Parkin1 signaling pathway
Melatonin prevents sepsis-induced renal injury via the PINK1/Parkin1 signaling pathway
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DOI：
10.3892/ijmm.2019.4306
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发表时间：
2019-10-01
影响因子：
5.4
通讯作者：
Deng, Yijun
中科院分区：
文献类型：
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作者：
Dai, Wenling;Huang, Haifeng;Deng, Yijun
褪黑激素（N-乙酰基-5-甲氧基色胺；MT）已被证明对脓毒症引起的肾损伤具有保护作用，然而，MT 功能的潜在机制仍有待阐明。因此，在本研究中，研究了 MT 在脓毒症引起的肾损伤中预防作用的潜在机制。采用苏木精和伊红染色检测 MT 对减轻肾组织损伤的作用，并通过免疫组织化学 (IHC)、ELISA 和蛋白质印迹分析确定 MT 对 PTEN 诱导的推定激酶 1 (PINK1)、核苷酸寡聚化结合结构域和富含亮氨酸的重复热蛋白结构域 3 (NLRP3)、含有 C 端的凋亡相关斑点样蛋白表达的影响。 caspase 募集结构域 (ASC1)、白细胞介素 (IL)-18、IL-1 beta、IL-6 和切割的 caspase-1。最后，采用TUNEL法比较假手术组、盲肠结扎穿刺组(CLP)和CLP+MT组肾组织的凋亡率。 CLP组组织损伤程度最高，假手术组组织损伤程度最低。 IHC和western blot分析显示，假手术组PINK1蛋白水平最高，而CLP组PINK1蛋白水平最低。相比之下，假手术组的NLRP蛋白水平最低，而CLP组的NLRP3蛋白水平最高。此外，CLP处理增强了ASC1和cleaved caspase-1的蛋白表达，而MT的施用在一定程度上降低了ASC1和cleaved caspase-1的蛋白表达。最后发现CLP组细胞凋亡率最高，假手术组细胞凋亡率最低。综上所述，在评价MT对脓毒症肾损伤的治疗作用时，本研究结果表明，MT通过调节大鼠体内PINK1、Parkin1、NLRP3、ASC和cleaved caspase-1的表达来减轻脓毒症肾损伤。
Melatonin (N-acetyl-5-methoxytryptamine; MT) has been shown to have a protective effect against sepsis-induced renal injury, however, the mechanisms underlying the function of MT remain to be elucidated. Therefore, in the present study, the potential mechanisms underlying the preventive role of MT in sepsis-induced renal injury were investigated. Hematoxylin and eosin staining was used to detect the effect of MT on the reduction of renal tissue damage, and immunohistochemistry (IHC), ELISA and western blot analysis were performed to determine the influence of MT on the protein expression of PTEN-induced putative kinase 1 (PINK1), nucleotide-oligomerization binding domain and leucine-rich repeat pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC1), interleukin (IL)-18, IL-1 beta, IL-6 and cleaved caspase-1. Finally, a TUNEL assay was used to compare the rate of apoptosis of renal tissues among the sham, cecal ligation and puncture (CLP), and CLP + MT groups. The extent of tissue damage in the CLP group was the highest and the extent of tissue damage in the sham group was the lowest. The IHC and western blot analysis showed that the sham group had the highest protein level of PINK1, whereas the CLP group had the lowest protein level of PINK1. By contrast, the sham group had the lowest protein level of NLRP, whereas the CLP group had the highest level of NLRP3. Furthermore, CLP treatment enhanced the protein expression of ASC1 and cleaved caspase-1, whereas the administration of MT reduced the protein expression of ASC1 and cleaved caspase-1 to a certain degree. Finally, the apoptotic rate was found to be the highest in the CLP group and the lowest in the sham group. Taken together, in evaluating the therapeutic effect of MT on sepsis-induced renal injury, the results of the present study showed that MT alleviated sepsis-induced renal injury by regulating the expression of PINK1, Parkin1, NLRP3, ASC and cleaved caspase-1 in rats.