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中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (5): 500-505.

• 基础研究 • 上一篇    下一篇

激动黑皮质素4型受体对抗脓毒症诱导的肾脏损伤

汪华学1, 李徽徽2, 柴继侠2, 于影3, 高琴3   

  1. 1蚌埠医学院第一附属医院重症医学科,蚌埠233004,安徽;
    2蚌埠医学院组织学与胚胎学教研室,
    3生理学教研室,蚌埠 233030,安徽
  • 收稿日期:2013-01-25 修回日期:2013-04-16 出版日期:2013-05-26 发布日期:2013-05-22
  • 通讯作者: 高琴,女,博士,副教授,研究方向:疾病损伤与修复。Tel: 0552-3175268 E-mail: bbmcgq@126.com
  • 作者简介:汪华学,男,硕士,副主任医师,研究方向:重症治疗与监护。Tel: 0552-3086167 E-mail: huaxuew@139.com
  • 基金资助:
    安徽省高等学校省级自然科学研究项目(KJ2012Z254)

Activation of melanocortin 4 receptor attenuate sepsis induced renal injury

WANG Hua-xue1, LI Hui-hui2, CHAI Ji-xia2, YU Ying3, GAO Qin3   

  1. 1Department of Intensive Care Unit, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233004,Anhui,China;
    2Department of Histology and Embryology,
    3Department of Physiology, Bengbu Medical College, Bengbu 233030, Anhui,China
  • Received:2013-01-25 Revised:2013-04-16 Online:2013-05-26 Published:2013-05-22

摘要: 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。

关键词: 脓毒症, 肾损伤, 黑皮质素4型受体, NF-κB, 大鼠

Abstract: 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.

Key words: Sepsis, Renal injury, Melanocortin 4 receptor, NF-κB, Rat

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