川芎嗪对严重烫伤大鼠早期肾脏p38MAPK TNF-α超微结构变化的影响

The effect of Tetra ethyl pyrazine on the p38MAPK,TNF-α,ultrastructure of the renal tissue in rats in the early stage after severe thermal injury

目的探讨川芎嗪对严重烫伤大鼠早期肾脏的保护作用与p38MAKP之间的关系。方法清洁级成年雄性Wistar大鼠88只,随机分为对照组、烫伤组和川芎嗪组,对照组(0h)8只;烫伤组和川芎嗪组各40只,后两组又分为1、3、6、12、24h五个时相点,采用Western blotting方法检测肾脏组织p38MAKP的活化水平,放射免疫法检测肾脏组织TNF-α及血清Cr的含量,电镜观察肾小管上皮细胞的超微结构变化。结果与对照组比较烫伤组伤后1h肾组织p38活化水平明显升高,3h达峰值(P<0.05),6h明显减弱,肾脏组织TNF-α含量在伤后6h开始增加,12h达峰值(P<0.05),24h仍较高;而反映肾小管上皮细胞超微结构异常变化也是从伤后6h开始出现,12h水肿最为严重,血清Cr在伤后1、3h一过性的升高,其他时点与对照组比较无明显差异,川芎嗪组上述指标要比烫伤组明显下降和减轻(P<0.05)。结论烧伤早期肾脏p38活化诱使肾组织TNF-α过度产生、释放,引起肾组织的损伤,川芎嗪通过抑制肾组织p38MAPK活化,从而减少肾脏组织TNF-α的产生,减轻肾小管上皮细胞的超微结构异常变化。

Objective To investigate Tetra Ethyl Pyrazine （TMP） blocking of the activated p38 mitogen-activated protein kinase （MAPK） and its protection capability for early stage severe thermal injury kidney in rats. Methods Eighty eight adult health rats were randomly divided into three groups： control group, burns group and burns ＋ TMP group （TMP group）. The control group had 8 rats. Forty （40） rats between both the burn group and the burn TMP group, then were respectively divided into five scheduled time points. The five scheduled time points were 1, 3, 6, 12, 24 hours post burn. We checked and measured the activated levels of p38MAPK and the content levels of TNF-ain the renal tissue, the creatinine content level in the serum and change of the ultrastructure of the renal tissue in rats. Reseults Compare the control group with both the burn group and the burn TMP group. The burn group and the burn TMP group have a high activated level of p38MAPK in the renal tissue tested at 1 hour post burn and the highest one occurred at 3 hours（P〈0.01-0.05）. A high level of TNF-αwas found at 6 hours post burn in renal tissue with the highest one at 12 hours （P〈0.01-0.05）. The abnormal change of ultrastrncture starts at 6 hours with the severe change at 12 hours, but the activated level of p38MAPK, the level of TNF-α, and abnormal change of uhrastrncture of TMP group are slighter than that of burn group（P〈0.01-0.05）. Conclusion These results indicated that the over activated levels of p38MAPK causes injury of the renal tissue in rats after early stage severe thermal injury; TMP protects against kidney injury by the possibility of blocking the activated level of p38 MAPK and content production in the renal tissue.