右美托咪定预处理对气腹所致大鼠肾脏损伤的保护作用

Protective effect of dexmedetomidine preconditioning on renal injury induced by pneumoperitoneum in rats

旨在确定右美托咪定预处理对CO_(2)气腹所致大鼠肾脏损伤的保护作用。试验将大鼠随机分为3组(n=6):对照(Sham)组、气腹(Pp)组、右美托咪定预处理(Dex)组。Sham组仅维持呼吸麻醉90 min;Pp组和Dex组给与15 mmHg压力建立CO_(2)气腹模型,持续时间90 min;Dex组气腹前30 min腹腔注射右美托咪定(50μg/kg)。气腹解除后6 h,收集血清和肾组织,观察光镜下肾脏组织病理学形态变化;利用试剂盒检测各组尿素氮(BUN)、肌酐(Cr)、丙二醛(MDA)和超氧化物歧化酶(SOD)的含量变化;通过ELISA法检测白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)的水平变化;应用RT-qPCR法检测GRP78、IRE1-α、XBP-1、CHOP和Caspase-12的基因表达水平。结果显示:与Sham组相比,Pp组肾组织损伤程度明显增加,BUN、Cr和MDA含量均极显著上升(P<0.01),SOD活力极显著下降(P<0.01);IL-1β、TNF-α和IL-6的水平也均显著上升(P<0.01);GRP78、IRE1-α、XBP-1、CHOP和Caspase-12的基因表达量均上调(P<0.01)。但与Pp组比,Dex组BUN、Cr和MDA含量均有所下降,SOD活力上升;IL-1β、TNF-α和IL-6的水平有所下降,GRP78、IRE1-α、XBP-1、CHOP和Caspase-12的基因表达量有所下调。上述结果表明,15 mmHg压力的CO_(2)气腹可以对大鼠肾脏造成损伤,而大鼠腹腔注射右美托咪定可以从多方面保护CO_(2)气腹所致的肾脏损伤。

The aim of this study was to determine the protective effect of dexmedetomidine preconditioning on renal injury induced by CO_(2)pneumoperitoneum in rats,and to provide an alternative intervention method for veterinary clinic to reduce laparoscopic pneumoperitoneum injury.Eighteen SD rats were randomly divided into three groups:control(Sham)group,pneumoperitoneum(Pp)group and dexmedetomidine pretreated(Dex)group.Rats in Sham group was maintained respiratory anesthesia for 90 min;rats in Pp and Dex groups were given 15 mmHg pressure to establish CO_(2)pneumoperitoneum model for 90 min;rats in Dex group were injected intraperitoneally with dexmedetomidine(50μg/kg)30 min before pneumoperitoneum.The rats were killed 6 h after pneumoperitoneum,and the serum and renal tissue were collected.The histopathological changes of kidney were observed under light microscope,the contents of urea nitrogen(BUN),creatinine(Cr),malondialdehyde(MDA)and superoxide dismutase(SOD)were detected by kit,and the levels of interleukin 1β(IL-1β),tumor necrosis factorα(TNF-α)and interleukin 6(IL-6)were detected by ELISA.The gene expression levels of GRP78,IRE1-α,XBP-1,CHOP and Caspase-12 were detected by RT-qPCR.The results showed that compared with Sham group,the injury degree of renal tissue in Pp group was significantly increased,the contents of BUN,Cr and MDA were significantly increased(P<0.01),the activities of SOD were significantly decreased,the levels of IL-1β,TNF-αand IL-6were also significantly increased(P<0.1),and the gene expressions of GRP78,IRE1-α,XBP-1,CHOP and Caspase-12were all up-regulated(P<0.1).However,compared with the Pp group,the contents of BUN,Cr and MDA decreased,the activity of SOD increased,the levels of IL-1β,TNF-αand IL-6decreased,and the gene expression of GRP78,IRE1-α,XBP-1,CHOP and Caspase-12also decreased in Dex group.In conclusion,CO_(2)pneumoperitoneum with 15mmHg pressure can cause kidney damage in rats,while intraperitoneal injection of dexmedetomidine can protect the kidney injury caused by CO_(2)pneumoperitoneum in many ways.