内皮素反义基因治疗门静脉高压症的研究

目的研究内皮素-1反义寡核苷酸（ET1-ASON）在内毒素（LPS）致门静脉高压中的作用.方法应用ET1-ASON预处理后将LPS以1 mg/kg体重腹腔注射大鼠,以正义、错义ET1-ASON和生理盐水作为对照,4 h后检测大鼠PVF、PVP、PVR和IVCP;应用放射免疫法、RT-PCR检测各组门静脉血和肝脏的ET1表达情况.结果ET1-ASON处理组大鼠门静脉血浆和肝脏组织ET1表达减低;PVR和PVP较对照组明显降低,PVF无明显改变.结论ET1-ASON在内毒素致门脉高压中主要通过降低PVR起作用.

Effects of endothelin-1 on portal hypertension induced by endotoxin in vivo

Objective To investigate the effects of endothelin-1(ET1)on portal hypertension induced by endotoxin.Methods The rats were intraperitoneally injected with different doses of LPS. PVP,IVCP,PVF and PVR were recorded 4 h after the injection.ET1 anti-sense oligonucleotide and cation lipofectamine were mixed and then injected into the portal vein of rats.Twelve hours later,1 mg/kg LPS was injected and PVP,IVCP and PVF were recorded again.The liver and portal blood samples were used to detect ET1 by radioimmunoassay.ET1 mRNA of the liver tissue was detected by RT-PCR.Results The PVF and PVP in the rats were obviously increased with the dose of LPS. PVR decreased and the decrease was not related to the dose of LPS.ET1 antisense oligonucleotide partially counteracted the effects of LPS on portal hemodynamics by decreasing PVR and PVP.LPS prompted the expression of ET1 in liver tissue and serum of the rats.Conclusions ET1 plays an im- portant role in portal hypertension induced by endotoxin through increasing PVR.ET1 antisense oli- gonucleotide can partially inhibit portal hypertension induced by LPS.