摘要
目的:探讨肠源性内毒素血症在肝窦毛细血管化形成中的作用及其可能机制.方法:♂Wistar大鼠40只,完全随机分为模型组(n=32)与正常对照组(n=8),采用复合因素致肝硬化大鼠模型.模型组分别在饲养第2,4,6,8周末,正常对照组在实验开始时,经肠系膜上静脉末端穿刺测PVP,肝脏HE、VG染色,肝脏免疫组织化学染色观察α-SMA、LN、TGF-β1的动态表达,测定外周血中的内毒素、TNF-α、ALT的动态变化,采用扫描电镜观察肝窦内皮细胞失窗孔情况.结果:模型组ALT在第2周末达到高峰(57.84±7.57IU/L),随后逐渐下降;内毒素在第2、4、6周末,各点呈递增趋势,到第8周末时略有下降;TNF-α在第2、4周末呈递增趋势,到第6周末时略有下降,第8周末时又逐渐升高,但各点组均较对照组明显升高(均P<0.05);模型组PVP在第2、4周末,各点呈递增趋势,到第6周末时略有下降,第8周末时又逐渐升高;肝窦内皮细胞扫描电镜结果示随着肝纤维化及硬化程度的加重,窗孔逐渐变小、变少至消失;LN、TGF-β1免疫组织化学染色结果示随着病变的发展,与对照组和同指标前一时间组相比阳性表达逐渐增强(均P<0.05).α-SMA免疫组织化学染色在第2、4、6周末,阳性表达逐渐增强,到第8周末时略有下降.结论:肝硬化大鼠发生了肠源性内毒素血症,其可使TGF-β1、TNF-α、LN等合成增多,促进肝窦内皮细胞去窗孔化,间接参与肝窦毛细血管化的形成.
AIM： To investigate the role ofintestinal endotoxemia in the pathogenesis of hepatic sinusoidal capillarization in hepatic cirrhosis and explore possible mechanisms involved. METHODS： Forty male Wistar rats were randomly divided into two groups： control group （n = 8） and experimental group （n = 32）. Hepatic cirrhosis was induced in rats using carbon tetrachloride （CCl4） and alcohol. Rats in the experimental group were killed at weeks 2, 4, 6 and 8, respectively, while those in the control group were executed at the beginning of the experiment. The portal venous pressure （PVP） was measured by cranial mesenteric vein cannulation. The degree of hepatic cirrhosis wasevaluated by hematoxylin and eosin （HE） staining and Van Gieson＇s （VG） staining. The expression of alpha-smooth muscle actin （α-SMA）, laminin （LN） and transforming growth factor-β1 （TGF-β1） in the liver was detected by immunohistochemistry. The dynamic changes in the levels of endotoxin, alanine transferase （ALT） and tumor necrosis factor-α （TNF-α） in plasma were monitored using various kits. The defenestration of liver sinusoidal endothelial cells （LSECs） was observed using a scanning electron microscope. RESULTS： In the experimental group, plasma ALT level reached its peak at week 2 （57.84 ± 7.57 IU/L） and thereafter decreased. Plasma endotoxemia level gradually increased from week 2 to 6, but slightly decreased at week 8. Plasma TNF-α level increased from week 2 to 4, slightly decreased at week 6, and increased again at week 8. At all time points, the values of the above parameters were significant higher in the experimental group than in the control group （all P〈0.05）. PVP showed the same tendency as TNF-α level, increasing from week 2 to 4, slightly decreasing at week 6, and increasing again at week 8. LSEC fenestration gradually shrank, lessened and disappeared from week 0 to 8. The expression levels of LN and TGF-β1 increased from week 0 to 8, significantly higher than those in the control group or at the previous time points in the same group （all P〈0.05）. The expression level of α-SMA increased from week 0 to 6, but slightly decreased at week 8. CONCLUSION： Intestinal endotoxemia occurs in hepatic cirrhosis rats, which can increase the synthesis of TNF-α, TGF-β1 and LN and promote LSEC defenestration. Intestinal endotoxemia may be indirectly involved in the development of hepatic sinusoidal capillarization.
出处
《世界华人消化杂志》
CAS
北大核心
2009年第30期3101-3108,共8页
World Chinese Journal of Digestology
关键词
肠源性内毒素血症
肝窦毛细血管化
门静脉高压
Intestinal endotoxemia Hepatic sinusoidal capillarization Portal hypertension
