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(phosphoinositide-3-kinase/ protein kinase B, PI3K/Akt)信号通路减少梗阻性黄疸（Obstructive jaundice，OJ）大鼠肝细胞凋亡的作用。方法 选取40只合格雄性清洁型Wistar大鼠，7-9周龄，体重为 220-270g。按照随机数字表法分为4组：LY294002+右美托咪定组(L组)、梗阻性黄疸组（OJ组）、右美托咪定组（D组）、假手术组（S组)。前三组需要制作大鼠梗阻性黄疸模型，S组仅开腹胆总管探查、游离。D组完成造模72h后在腹腔注射右美托咪定注射液，剂量为：100ug/kg, S组和OJ组于同一时间点注射等容量0.9%无菌生理盐水，L组在给Dex10分钟前经尾静脉缓慢泵入PI3K抑制剂LY294002(10%DMSO配置10mmol/L） 0.3mg/kg。四组大鼠于注药3小时后取肝右外叶1.0cm ×1.0cm× 0.5cm 2份，HE染色观察肝组织病理学变化；TUNEL法测定肝细胞凋亡指数（AI）；Western Blot 法检测肝组织 Akt、磷酸化Akt(p-Akt)的表达水平；免疫组化法测定肝组织 Bcl-2及Bax 阳性细胞计数。结果 D组肝脏组织病理学损伤较L和OJ组减轻； OJ组较S组大鼠肝细胞TUNEL检测值、p-Akt、Bcl-2降低,Bax升高； D组较OJ组大鼠肝细胞TUNEL检测值、p-Akt、Bax降低,Bcl-2升高；L与D组相比，其大鼠肝细胞TUNEL检测值、p-Akt、Bcl-2降低,Bax升高。结论 右美托咪定可通过激活PI3K/Akt信号通路减少梗阻性黄疸时肝细胞凋亡。

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.

内蒙古自治区卫生计生科研计划（201701070）