右美托咪定通过PI3K/Akt信号通路减轻梗阻性黄疸大鼠肝细胞凋亡

目的:探究右美托咪定(dexmedetomidine,Dex)通过磷脂酰肌醇-3-激酶/蛋白激酶B(phosphoinosit-ide-3-kinase/protein kinase B,PI3K/Akt)信号通路减少梗阻性黄疸(obstructive jaundice,OJ)大鼠肝细胞凋亡的各种作用.方法:选取40只...

Dexmedetomidine alleviated the apoptosis of rat hepatocytes with obstructive jaundice through the PI3K/Akt signaling pathway

Objective to investigate the role of Dexmedetomidine (Dex) in reducing the apoptosis of Obstructive jaundice (OJ) rat hepatocytes through the phosphoinositide-3-kinase/ protein kinase B(PI3K/Akt) signaling pathway. Methods 40 qualified male clean Wistar rats were selected, weighing 220-270g at 7-9 weeks of age. According to the random number table method, they were divided into 4 groups: LY294002+ dexmedetomidine group (group L), obstructive jaundice group (OJ group), dexmedetomidine group (group D), and sham operation group (group S). The first three groups needed to make the rat model of obstructive jaundice, while the S group only had open common bile duct exploration and dissociation. Group D was intraperitoneally injected with dexmedetomidine injection at a dose of 100ug/kg after 72h of model building, group S and OJ were injected with 0.9% sterile normal saline of equal volume at the same time point, and group L was slowly pumped with PI3K inhibitor LY294002(10%DMSO with 10mmol/L) through tail vein at 0.3mg/kg 10 minutes before dexing. Two portions of the right lateral lobe of the liver (1.0cm× 1.0cm× 0.5cm) were taken from the four groups 3 hours after injection, and the histopathological changes of the liver were observed by HE staining. The apoptosis index (AI) of hepatocytes was determined by TUNEL assay. The expression levels of Akt and phosphorylated Akt(p-akt) in liver tissue were detected by Western Blot. The cell counts of bcl-2 and Bax in liver tissue were determined by immunohistochemistry. Results the liver histopathological injury in group D was less than that in group L and OJ. Compared with the S group, the TUNEL value, p-akt and bcl-2 of rat hepatocytes in OJ group decreased, while Bax increased. Compared with OJ group, the TUNEL detection value, p-akt and Bax of rat hepatocytes in group D decreased, while bcl-2 increased. Compared with group D, the TUNEL value, p-akt and bcl-2 of rat hepatocytes were decreased, while Bax was increased. Conclusion dexmedetomidine can reduce hepatocyte apoptosis in patients with obstructive jaundice by activating the PI3K/Akt signaling pathway.