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Ro27-3225组、盲肠结扎穿孔组(CLP)和CLP+Ro27-3225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+Ro27-3225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.