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| Effect of melatonin on acute kidney injury and miR-146a level in septic mice |
| ZHANG Jianing1 CAO Mengyuan2 LI Lincheng1 LIU Mingchuan1 LIU Yang3 HE Ting3▲ |
1.School of Basic Medicine, the Fourth Military Medical University, Shaanxi Province, Xi′an 710032, China;
2.Emergency Department, Xijing Hosptital, the Fourth Military Medical University, Shaanxi Province, Xi′an 710032, China;
3.Department of Burns and Cutaneous Surgery, Xijing Hosptital, the Fourth Military Medical University, Shaanxi Province, Xi′an 710032, China |
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Abstract Objective To investigate the effect of melatonin (MT) on apoptosis of renal cells and inflammation in lipopolysaccharide (LPS)-induced septic mice, and to explore the effect of MT on renal injury in sepsis as well as the role that microRNA-146a(miR-146a) plays. Methods Forty-eight male Balb/c mice were divided into sham-operated group (Sham group), MT treatment group (MT group) and placebo group (NS group) according to random number table method, with 16 mice in each group. Mice in the latter two groups were injected with LPS (10 mg/kg body weight) intraperitoneally to prepare sepsis model. Mice in MT group were injected with MT (30 mg/kg body weight) three times separately at half an hour before LPS injection, the same time as LPS injection and 4 hours after injection. At the same time，mice in NS group and Sham group were injected with same volume saline. After LPS treatment for 24 hours, the levels of interleukin (IL)-1β and IL-6 mRNA, miR-146a, the expression of apoptotic proteins Caspase-3 and Bax, serum creatinine (Cr) and urea nitrogen (BUN) were detected. After LPS treatment for 72 hours, the renal pathological changes and injuries of mice in each group were observed. Results ①The renal structure was normal in Sham group. The renal tubules in NS group were of tubular type, with unclear tubular structure, glomerular pyknosis, and a large number of inflammatory cells infiltrating; the number of necrotic glomeruli in MT group was much less than that in NS group. ②The levels of serum Cr and BUN in NS group were significantly higher than those in Sham group (P ＜ 0.01). The levels of Cr and BUN in MT group mice were significantly lower than those in NS group (P ＜ 0.01). ③The levels of Cleaved-caspase 3 and Bax in MT group mice were significantly lower than those in NS group (P ＜ 0.01). ④The levels of IL-1β and IL-6 in these three groups mice had statistically significant difference (P ＜ 0.05). In MT group, the levels of IL-1β and IL-6 in renal tissues were lower than those in NS group (P ＜ 0.01). ⑤The levels of miR-146a in renal tissues were highly statistically different in these three groups mice (P ＜ 0.01). In MT group, it was significantly higher than that in NS group (P ＜ 0.01). Conclusion MT can significantly improve renal injury in LPS-induced septic mice, which may related to the upregulation of miR-146a and suppression of inflammation and cell apoptosis.
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