P38和JNK丝裂原活化蛋白激酶在急性百草枯中毒大鼠肾脏中的表达及褪黑素的影响

The expressions of P38 mitogen-activated protein kinases and JNK mitogen-activated protein kinases in the renal tissue of rats with acute paraquat poisoning and the therapeutical effects of melatonin

目的 观察急性百草枯中毒大鼠肾脏P38蛋白激酶（mitogen-activated protein kinases,P38 MAKP）和JNK蛋白激酶（mitogen-activated protein kinases,JNK MAKP）的表达及褪黑素的影响,研究P38和JNK信号转导通路在百草枯中毒肾损伤中所起的作用.方法 将78只（雌性39只,雄性39只）成年健康SD大鼠随机分成对照组（6只）、染毒组（36只）、治疗组（36只）,给染毒组、治疗组一次性腹腔注射百草枯25 mg/kg,对照组腹腔内注射等量生理盐水,治疗组腹腔内注射褪黑素10 mg/kg,每天1次.染毒组、治疗组于注药后1、3、5、7、10、14天光学显微镜观察病理学改变,采用免疫组化方法观察肾组织中P38 MAKP和JNK MAKP的表达.结果 与对照组比较,各时间点染毒组大鼠肾组织中P38 MAKP表达高于对照组,第1天明显表达,10天达到高峰,14天虽有下降,仍高于对照组,差异均有统计学意义（P＜0.01）;各时间点染毒组大鼠肾组织中JNK MAPK表达高于对照组,第1天达到高峰,以后维持在高水平,至14天仍高于对照组,差异均有统计学意义（P＜0.01）.治疗组各时间点P38 MAPK和JNK MAPK的表达低于染毒组,高于对照组,差异均有统计学意义（P＜0.05或P＜0.01）.结论 P38 MAKP和JNKMAKP在百草枯中毒大鼠肾组织表达增高,褪黑素能明显降低P38MAPK和JNKMAPK在肾组织的表达,可能与褪黑素较强的抗氧化功能有密切关系.

Objective To investigate the expressions of P38 mitogen-activated protein kinases （P38 MAPK）,JNK mitogen-activated protein kinases（JNK MAPK） and the therapeutical effects of melatonin in the renal tissue of acute acuteparaquat-induced rats.Methods Seventy-eight healthy adult Sprague-Dawley （SD） rats （39 male,39female） were randomly divided into three groups：（1） Control group （group A）：6 rats,（2） Poisoned group （group B）：36 rats,（3）Therapeutical group （group C）：36 rats.At 1、3、5、7、10 and 14 days after poisoning,six rats in Group B and group C were used to assess renal pathological changes and the expression of P38 MAPK、JNK MAPK in kidney were evaluated by immunohistochemistry.Results Compared with control group,the expression of P38MAPK in renal tissue of poisoned group significantly rose at the first day,reached the peak at the 10th day and afterwards decreased slowly.Expression ofJNK MAPK reached the peak at the first day,and kept at relatively high levels up to the 14th day.Melatonin weakened markedly the expressions of P38 MAPK and JNK MAPK in renal tissue of acute acuteparaquat-induced rats.Conclusion P38 MAPK and JNK MAPK play an important role in renal injury of acute paraquat-poisoning rats.Melatonin takes a significant effect on the activation of them.