谷氨酰胺对内毒素血症幼年大鼠肾脏ERK以及p38表达的影响

Effects of glutamine on extracellular signal regulated kinase and p38MAPK expression in the kidney in young rats with endotoxemia

目的通过观察谷氨酰胺(glutamine,Gln)对内毒素血症幼年大鼠肾脏信号转导通路ERK-2、p38及其mRNA表达的影响,探讨谷氨酰胺在大鼠内毒素血症中通过干预肾脏ERK-2以及p38信号转导途径来保护肾脏的机制。方法选健康18日龄Wistar大鼠121只,按腹腔注射药物不同分为:0 h对照组(生理盐水,n=11),内毒素组(LPS,n=55),谷氨酰胺组(Gln,n=55);后两组又分为2,4,6,24及72 h共5个时间点,每个时间点11只,在各指定时间点分别将大鼠断头分离肾脏,8只用逆转录-聚合酶链反应(RT-PCR)方法测定ERK-2以及p38的mRNA的表达,另3只取肾组织后用甲醛固定,制成石蜡切片,用免疫组化方法确定ERK-2以及p38蛋白质的表达。结果LPS组各时点ERK-2 mRNA,p38MAPK mRNA,ERK-2,p38MAPK表达均较对照组增强,最高点在6 h,差异有显著性,P<0.01;Gln组各时点ERK-2 mRNA,p38MAPK mRNA,ERK-2,p38MAPK表达趋势与LPS组一致,但明显低于LPS组,P<0.05或P<0.01。结论ERK及p38在内毒素血症表达均明显增强。谷氨酰胺可使其表达下调,从而减轻肾脏损伤。

Objective Glutamine has protective effects against renal injuries. This study was designed to explore the possible mechanism underlying the protections by examining the effects of glutamine on extracellular signal regulated kinase （ERK） and p38MAPK expression in the kidney in rats with endotoxemia. Methods One hundred and twenty-one 18-day- old Wistar rats were randomly injected with LPS （d mg/kg; n =55）, LPS （4 mg/kg） ＋ glutamine （1 mI/kg） （n =55）, or normal saline （ control group ; n = 11 ）. The two LPS groups were subdivided into five groups sacrificed at 2, 4, 6, 24 and 72 hrs after administration （n = 11 each ）. ERK-2 and p38MAPK mRNA and protein expression in the kidney were measured by RT-PCR and immunohistrochemistry. Results Compared to the control group, the mRNA and protein expression of both ERK-2 and p38MAPK in the LPS group significantly increased 2, 4, 6, 24 and 72 hrs after administration （P 〈0. 01 ）, and reached a peak at 6 hrs （P 〈0.01 ）. In the LPS ＋ glutamine group, the trend of ERK-2 and p38MAPK expression was similar to the LPS group but their expressional levels were significantly lower than those in the LPS group at all time points （P 〈 0.05 or 0. 01 ）. Conclusions Both ERK-2 and p38MAPK expression increased in young rats with LPS-induced endotoxemia. Glutamine alleviates renal injuries possibly by decreasing the expression of both.