目的研究肝硬化门静脉高压症(PHT)患者肠系膜微动脉对去甲肾上腺素收缩反应性的变化,探讨PHT内脏血管低反应的机制,以及RhoA/ROCK通路改变所产生的作用机制。方法取2010年1月至2011年6月在我院普外科或肝移植科手术治疗的患者,PHT组7例,非PHT组8例。术中测门静脉压力,取空肠旁第三级肠系膜血管,利用血管灌流系统测定肠系膜微动脉对去甲肾上腺素的反应,运用Westernblotting法测定RhoA/ROCK通路中相关蛋白量的表达以及活性的改变。结果PHT患者的离体肠系膜微动脉对去甲肾上腺素剂量反应曲线右移,EC50高于非PHT患者(P〈0.01);与非PHT患者相比较,肝硬化PHT患者的肠系膜动脉RhoA蛋白量无明显变化(P〉0。05),但是ROCK-1蛋白量和活性却明显降低(P〈0.01)。结论肝硬化PHT患者肠系膜动脉对缩血管物质的反应性降低,RhoA/ROCK信号通路受损参与了该反应。
Objective To study the changes of PHT superior mesenteric arteriole on the contractile response to norepinephrine with cirrhosis caused by hepatitis B. The mechanism of RhoA/ROCK pathway mechanism in PHT was also explored. Methods Clinical patients were chosen who received operations because of PHT with cirrhosis caused by hepatitis B and non-PHT patients due to other benign diseases at the Department of General Surgery and Transplantation Surgery in our hospital from January 2010 to June 2011. Non-PHT group contains 8 cases, 4 cases of common bile duct stones, and 4 cases of choledochal cyst; 7 cases were of PHT with cirrhosis caused by hepatitis B. Intraoperative measurement of portal pressure was measured. Took the third level intestinal mesentery vessels with their mesentery next to the jejunum and studied the contractile response to norepinephrine of the intestinal mesenteric arterioles. RhoA/ROCK pathway associated proteins' expression and activity changes were measured by Western blotting method. Results The dose-response curve of isolated mesenteric arterioles to norepinephrine from PHT patients with cirrhosis shifted to the right, and the ECs0 value was higher than that of non-PHT patients (P〈0.01). Compared with that of non-PHT patients, the protein of RhoA in mesenteric arteries of PHT patients with cirrhosis did not change significantly (P〉0.05), but the protein express and activity of ROCK-1 were signifi- cantly reduced (P〈0.01). Conclusion superior mesenteric arteriole on the contractile response to vasocontrictive agents decrease in PHT with cirrhosis, and the impaired RhoA/ROCK pathway is involved in this reaction.