激动黑皮质素4型受体对抗脓毒症诱导的肾脏损伤

目的:观察激动黑皮质素4型受体(MC4R)对抗脓毒症诱导的肾脏损伤作用,并探讨其机制.方法:雄性SD大鼠24只,随机分为:假手术组(Sham)、Sham+MC4R激动剂R027-3225组、盲肠结扎穿孔组(CLP)和CLP+R027-3225组,造模24 h后测定血清尿素氮(BUN)和肌酐(CRE)水平,HE染色观察肾脏形态学变化,免疫组化观察肾小管细胞NF-κB P65的表达,RT-PCR测定肾脏组织NF-κB mRNA表达情况.结果:与Sham组相比,CLP组血清BUN和CRE水平明显升高(P＜0.01),组织切片显示CLP组大鼠肾小体中血管球淤血、皱缩、肾小囊腔扩大,伴肾小管上皮细胞肿胀和坏死.肾脏组织NF-κB P65表达呈强阳性,NF-κB mRNA表达增高(P＜0.01).与CLP组相比,CLP+R027-3225组BUN和CRE水平下降(P＜0.01),肾小体、肾小管损伤减轻,肾脏组织NF-κB P65表达和NF-κB mRNA表达下降(P＜0.01).结论:脓毒症大鼠肾脏功能受损,激动MC4R可对抗脓毒症诱导的肾脏损伤,这可能与减少NF-κB的表达,降低炎症反应有关.

Activation of melanocortin 4 receptor attenuate sepsis induced renal injury

AIM： To observe the effect of activation of melanocortin 4 receptor（MC4R） against sepsis induced renal injury and analyze the related mechanism.METHODS： Twenty four male SD rats were divided into 4 groups： Sham group,Sham＋Ro27-3225（the activator of MC4R） group,CLP group and CLP＋Ro27-3225 group.CLP model was established by cecal ligation and puncture operation.Serum creatine（CRE）,blood urea nitrogen（BUN） levels were measured and renal structural changes were observed by HE staining 24 h after CLP and NF-κB P65 expression in kidney tubules was measured by immunohistochemical method.The mRNA expression of NF-κB in kidney was determined by RT-PCR.RESULTS：Compared with Sham group,the levels of CRE and BUN were significantly increased（P〈0.01）,renal corpuscle was congested and wrinkled,capsular space was enlarged accompanying with epithelial cell swelling and necrosis.The expressions of NF-κB P65 protein and NF-κB mRNA level were increased（P〈0.01）.Compare with CLP group,the levels of CRE and BUN were decreased（P〈0.01） in CLP＋Ro27-3225 group,the damage of renal corpuscle and tubule was attenuated.The expression of NF-κB P65 protein and NF-κB mRNA level were decreased（P〈0.01）.CONCLUSION： Sepsis induced renal injury in rat CLP model,Activation of MC4R attenuated renal injury,which may be associated with decreasing NF-κB expression and reducing inflammatory reaction.