谷氨酰胺对脓毒症幼年大鼠心肌ERK_2mRNA以及p38MAPK表达的影响

Effects of glutamine to extracellular signal regulated kinase mRNA and p38MAPK expressions of myocardial in rat with sepsis

目的观察脓毒症心肌细胞外信号调节激酶(extracellularsignalregulatedkinase-2,ERK2)和丝分裂原蛋白激酶(mitogenactivatedproteinkinase,p38MAPK)是否参与这一病理过程,以及谷氨酰胺(Glutamine,Gln)对其表达的影响,探讨Gln对脓毒症大鼠心肌的保护途径。方法选健康18日龄Wistar大鼠88只,按腹腔注射药物不同生理盐水作对照组(0h),内毒素(LPS)、Gln组,各组于加LPS后2、4、6、24及72h分别取8只,断头无菌分离心脏,4%多聚甲醛固定12￣16h,制成石蜡切片,用原位杂交方法测定ERK2mRNA表达,用免疫组化方法测定p38MAPK表达。结果LPS组各时点ERK2mRNA以及p38MAPK表达均较对照组增强,最高点分别在6h和6￣24h,差异有显著性,P<0.01;Gln组各时点ERK2mRNA以及p38MAPK表达趋势与LPS组一致,但明显低于LPS组,P<0.01。结论ERK2mRNA以及p38MAPK表达在脓毒症时均明显增强;谷氨酰胺可以使其表达下调。

[Objective] To examine if glutamine （Gln） protect myocardial by depressing the expression both extracellular signal regulated kinase （ERK） and p38MAPK in rat with sepsis. [Methods] 88 Wistar 18-day-rats endotoxemia model were established first by intraperitoneal injection of a dose of normal saline （8 rats） /LPS （40 rats） （4 mg/kg, Eseherichia coli O55：B5 ） / LPS 4 mg/kg ＋ Gln 1mL/kg （40 rats）, then sacrificed after 2, 4, 6, 24 and 72 h thereafter, the hearts were isolated and fixed by 4% formaldehydum polymerisatum to measure the expressions of ERK2 mRNA by in situ hybridization and MAPK by immunohistrochemistry. [Results] Compared to control, the expressions of both ERK2 mRNA and p38MAPK in LPS group were significantly enhanced at every point hours, especially at 6 h and 6 to 24 h respectively （P 〈0.01）, then they gradually recovered, but till 72 h, they still higher than those at 0 h （P 〈0.01）, while in Gln group, the trend of ERK2 mRNA and p38MAPK expressions were similar to but significantly lower than those in LPS group at every points, the highest point were at 6 h and 6 to 24 h respectively （P 〈0.01）, then they gradually declined, but till 72 h, they still higher than those at 0 h （P 〈0.01）. [Conclusion] Both ERK2 mRNA and p38MAPK join in LPS-induced endotoxemia, glutamine down-regulated the expression both ERK2 mRNA and p38MAPK.