右美托咪定对腹腔镜气腹致大鼠肠损伤的影响

Effect of dexmedetomidine on intestinal injury in rats induced by laparoscopic pneumoperitoneum

旨在探讨右美托咪定对气腹所致肠损伤的保护作用。将18只SD大鼠分为3组(6只/组):假手术组(Sham)、CO_(2)气腹组(CO_(2))、右美托咪定组(DEX)。CO_(2)组和DEX组在2 kPa(15 mmHg)气腹压力下维持90 min建立气腹模型;DEX组在气腹前30 min腹腔注射50μg/kg右美托咪定;Sham组不通气腹,其余操作同CO_(2)组。气腹结束6 h收集小肠样本。通过HE染色观察小肠组织病理形态学变化;采用ELISA法检测IL-6、IL-1β、TNF-α水平;化学发光法检测MDA、GSH含量和MPO活性;采用RT-qPCR检测紧密连接蛋白ZO-1、Occludin和Claudin-1的mRNA表达;Western blot检测HO-1、Nrf2、IKBα、NF-κB蛋白表达。结果显示:与Sham组相比,CO_(2)组IL-6、IL-1β、TNF-α、MDA含量和MPO活力均极显著升高(P<0.01),GSH含量极显著降低(P<0.01),ZO-1、Occludin、Claudin-1的mRNA相对表达量均极显著降低(P<0.01),HO-1、Nrf2、IKBα和NF-κB的蛋白表达极显著升高(P<0.01);与CO_(2)组相比,DEX组IL-6、IL-1β、TNF-α、MDA含量和MPO活力均极显著下降(P<0.01),GSH含量极显著升高(P<0.01),ZO-1、Occludin、Claudin-1的mRNA相对表达量极显著升高(P<0.01),HO-1、Nrf2蛋白表达极显著升高(P<0.01),IKBα蛋白表达极显著下降(P<0.01),NF-κB蛋白表达显著下降(P<0.05)。上述结果表明,右美托咪定可以通过抗氧化、降低炎性反应等减轻腹腔镜气腹所致肠损伤。

The aim of this experiment was to investigate the protective effect of dexmedetomidine on pneumoperitoneum-induced intestinal injury.In this experiment,18 SD rats were divided into 3groups(6 rats/group):sham-operated group(Sham),CO_(2) pneumoperitoneum group,and dexmedetomidine group(DEX).The CO_(2) and DEX groups were maintained at 15 mmHg pneumoperitoneum pressure for 90 min to establish the pneumoperitoneum model;the DEX group was injected with 50μg/kg dexmedetomidine intraperitoneally 30 min before pneumoperitoneum;the Sham group had no pneumoperitoneum and the rest of the operation was the same as the CO_(2) group.The small intestine samples were collected 6 h after the end of pneumoperitoneum.The histomorphological changes of small intestine were observed by HE staining;IL-6,IL-1β and TNF-α levels were detected by ELISA;MDA,GSH content and MPO activity were detected by chemiluminescence;mRNA expression of tight junction proteins ZO-1,Occludin and Claudin-1 were detected by RTqPCR;HO-1,Nrf2,IKBα and NF-κB protein expression were detected by Western blot.The results showed that compared with the Sham group,the CO_(2) group showed highly significant increases in IL-6,IL-1β,TNF-α,MDA content and MPO activity(P<0.01),highly significant decreases in GSH content(P<0.01),highly significant decreases in the relative mRNA expressions of ZO-1,Occludin and Claudin-1(P<0.01),and highly significant increases in HO-1,Nrf2,IKBαand NF-κB protein expressions were highly significantly increased(P<0.01).Compared with the CO_(2)group,the DEX group showed a highly significant decrease in IL-6,IL-1β,TNF-α,MDA content and MPO activity(P<0.01),a highly significant increase in GSH content(P<0.01),a highly significant increase in the relative mRNA expression of ZO-1,Occludin and Claudin-1(P<0.01),and a highly significant increase in HO-1,Nrf2 protein expression was highly significantly elevated(P<0.01),IKBαprotein expression was highly significantly decreased(P<0.01),and NF-κB protein expression was significantly decreased(P<0.05).These results suggest that dexmedetomidine can reduce intestinal injury due to laparoscopic pneumoperitoneum by antioxidant and reducing inflammatory response.