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血管活性物质在肝硬化肝移植后高血流动力学中的作用

The role of vasoactive substance in hyperhemodynamics after orthotopic liver transplantation in cirrhotic rats

摘要目的 探讨内源性血管活性物质在肝硬化鼠肝移植后高血流动力学中的作用。 方法雄性SD大鼠随机分为四组:正常对照组(NL)、肝硬化组(IHPH)、正常鼠肝移植组(NL-OLT)和肝硬化鼠肝移植组(IHPH-OLT)。IHPH-OLT鼠又分为术后3天(A组)和7天(B组)两个亚组。IHPH模型肌注CCl4制备,大鼠OLT模型采用三袖套法。血流动力学研究采用放射性微球注射技术。血浆胰高糖素(Glu)、一氧化氮(NO)、前列环素(PGI2)、血栓素(TXA2)以及内皮素(ET)浓度用放射免疫法测定。 结果 NL-OLT鼠绝大多数血流动力学参数与NL鼠比较差异无显著意义(P>0.05)。与NL鼠比较,NL-OLT鼠的NO和PGI2均无明显变化,而Glu、ET和TXA2水平显著地升高(P<0.05)。IHPH、IHPH-OLTA、B鼠均具有全身和内脏高血流动力学特征,其高动力循环的程度和血管扩张物质NO和Glu增加的程度均是IHPH>IHPH-OLTA>IHPH-OLTB鼠。IHPH鼠的PGI2显著地高于NL鼠,IHPH-OLTA、B鼠的PGI2显著地低于IHPH鼠(P<0.05),而IHPH-OLTB鼠与NL鼠比较已无显著差异。血管收缩物质ET和TXA2在肝硬化肝移植术后均有不同程度升高。 结论 肝移植术本身并不导致术后高血流动力学的发生。血管扩张物质NO和Glu,尤其是NO在IHPH以及IHPH-OLT鼠的高动力循环中起重要作用。肝硬化肝移植后早期依然存在的高动力循环是术前引起高血流动力学发病因子升高的原因未消除的结果。

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abstractsObjective To evaluate the role of endogenous vasoactive substancein hyperdynamic circulation after orthotopic liver transplantation (OLT) in cirrhotic rats. Methods Male SD rats were divided into 4 groups: normal controls (NL,10 rats), intrahepatic portal hypertension induced by injection of CCl4 (IHPH,10), normal rats with OLT (NL-OLT, 9), and IHPH rats with OLT (IHPH-OLT, 16). IHPH-OLT rats were divided into 2 subgroups: 3 days (Group A, 9 rats) and 7 days (Group B, 7) after OLT. OLT was performed in rats by using cuffs for the anastomosis of suprahepatic inferior vena cava, infrahepatic vena cava, and portal vein. Radioactive microsphere method was used for hemodynamic study.The concentrations of plasma glucagon(Glu), nitric oxide(NO), prostaglandin(PGI2, TXA2) and endothelin (ET) were measured by radioimmunoassay. Results No significant difference of hemodynamic changes was observed between NL-OLT and NL rats except mean arterial blood pressure. No significant changes of NO, PGI2 were seen between NL-OLT and NL rats. Glu, ET and TXA2 in NL-OLT rats were significantly elevated as compared to those in NL rats (P<0.05). There were characteristics of systemic and splanchnic hyperdynamic circulatory state in IHPH, IHPH-OLT A, IHPH-OLT B rats. Both the magnitude of hyperhemodynamics and increased concertrations of Glu and NO were in the order of IHPH>IHPH-OLT A>IHPH-OLT B rats. The level of plasma PGI2 in IHPH rats was significantly elevated compared to NL rats, while PGI2 in IHPH-OLT A rats, B was found significantly lower than that in IHPH rats (P<0.05). There was no significant difference of PGI2 between IHPH-OLT B and NL rats. Vasoconstrictors including ET and TXA2 were found elevated in IHPH-OLT rats. Conclusions Vasodilators including NO and Glu, especially NO play an important role in the hyperhemodynamics in IHPH and IHPH-OLT rats. The results of present study demonstrate that persistence of early systemic and splanchnic hyperkinetic circulation after OLT may be that the consequence of the factors maintaining hyperhemodynamics in liver cirrhosis with portal hypertension is not completely eliminated, while hyperhemodynamics is not induced by OLT perse.

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