【摘要】 目的观察褪黑素对急性百草枯中毒大鼠肾组织中Caspase-3表达及血浆中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平的影响,探讨急性百草枯中毒导致肾损伤的机制。方法将126只SD大鼠随机分成正常组、染毒组、干预组,染毒组及干预组一次性腹腔内注射百草枯25 mg/kg建立中毒模型,正常组注射等量0.9%氯化钠,之后干预组每天腹腔内注射褪黑素10 mg/kg,正常组及染毒组腹腔内注射等量0.9%氯化钠,均1次/d。在实验的1,3,7,14,21,28,35 d,每组各取6只,腹主动脉采血检测血浆中TNF-α、IL-6水平;留取肾组织标本,采用免疫组化法检测Caspase-3表达情况,采用TUNEL染色法检测肾小管上皮细胞凋亡率。结果染毒组各时间点血浆TNF-α、IL-6水平均明显高于正常组(P均<0.05);干预组各时间点血浆TNF-α、IL-6水平均明显低于染毒组(P均<0.05),但各时间点TNF-α水平和1,3,7,14,21 d IL-6水平仍明显高于正常组(P均<0.05)。染毒组各时间点肾组织中Caspase-3蛋白表达量及细胞凋亡率均明显高于正常组(P均<0.05),干预组Caspase-3蛋白表达量及细胞凋亡率均明显低于染毒组(P均<0.05),但各时间点Caspase-3蛋白表达量和7,14,21,28 d细胞凋亡率仍明显高于正常组(P均<0.05)。结论 TNF-α、IL-6及Caspase-3在百草枯所致大鼠肾损伤中起重要作用;褪黑素能减少染毒大鼠血浆中TNF-α、IL-6的产生,抑制肾组织细胞Caspase-3的表达,降低其调控的细胞凋亡率,减轻染毒大鼠肾组织损伤。更多还原

【Abstract】 Objective It is to explore the effects Melatonin on expression of Caspase-3 in renal tissues and plasma level of TNF-α and IL-6 in acute paraquat-induced rats so as to investigate the renal injuring mechanism by paraquat. Methods One hundred and twenty-six adult healthy Sprague-Dawley( SD) rats were randomly divided into 3 groups: control group,poisoned group,treatment group. The rats in poisoned group and treatment group were injected with paraquat( 25 mg/kg) intraperitoneally to establish poisoned models,the rats in control group were injected with the same dose of normal saline. Then treatment group was given Melatonin 10 mg/kg intraperitoneally,control group and poisoned group were given the same dose of normal saline intraperitoneally,all once per day. On 1st,3rd,7th,14 th,21st,28 th and 35 th day,6 rats from each group were selected,then their blood from abdominal artery was gotten to detect the levels of TNF-α and IL-6 in serum,renal tissue specimen was made to detect the expression of Caspase-3 by immunohistochemical assay,and apoptosis of renal tubular epithelial cells was observed by TUNEL staining method. Results Compared with control group,the levels of TNF-α and IL-6 in serum of poisoned group increased significantly at all time points( P < 0. 05),and the levels in treatment group were significantly lower than that in poisoned group at all time points( P < 0. 05),but the level of TNF-α at every time point and that of IL-6 on1 st,3rd,7th,14 th,21st day were still higher than that in control group( P < 0. 05). Caspase-3 expression and cell apoptosis in renal tissue markedly raised at every time point in poisoned group compared with control group( P < 0. 05),these indexes in treatment group were lower than that in poisoned group( P < 0. 05),but the expression of Caspase-3 at every time point and cell apoptosis on the 7th,14 th,21st,28 th day were still higher than that in control group( P < 0. 05). Conclusion TNF-α,IL-6 and Caspase-3 may play an important role in renal injury of paraquat-poisoning rats. Melatonin can reduce the production of TNF-α and IL-6 in poisoned rat plasma,inhibit the Caspase-3 expression in renal tissues,decrease the rate of renal cell apoptosis,relieve the injury in renal tissue of acute paraquat-poisoning rats.更多还原