不同程度梗阻性黄疸对大鼠肝切术后肝再生影响的实验研究
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摘要
目的探讨术前不同程度梗阻性黄疸对大鼠肝切除术后肝再生的影响,为临床应用提供理论依据。
方法建立梗阻性黄疸SD大鼠模型,测定梗阻不同时相的黄疸水平,并根据黄疸不同水平分组:1.SO-Hx组:正常大鼠肝切除组,2.OJ1-Hx组:梗阻性黄疸1天肝切除组,3.OJ3-Hx组:梗阻性黄疸3天肝切除组,4.OJ7-Hx组:梗阻性黄疸7天肝切除组;观察肝切除术后动物死亡率、残肝重/体重的比值、生化检测术后肝功、免疫组化检测术后肝组织PCNA标记指数、RT-PCR检测肝组织HGF mRNA的表达情况。
结果胆总管结扎诱导的胆道梗阻SD大鼠血清总胆红素呈进行性升高,在梗阻168h(7d)达峰值(约85倍)后缓慢下降。胆道梗阻后行肝切除术后死亡率升高,OJ1-Hx组、OJ3-Hx组和OJ7-Hx组的死亡率分别为6.67%、26.67%和46.67%,明显高于对照组(0%);OJ3-Hx组和OJ7-Hx组肝切除术后168h(7d)的右叶肝重/体重比值明显低于SO-Hx组,差别有显著性(p<0.05),而OJ1-Hx组接近SO-Hx组,差别无显著性(p>0.05);OJ3-Hx组和OJ7-Hx组肝切除术后肝功恢复缓慢,术后0-168h与SO-Hx组相比,差别均有显著性(p<0.05);而OJ1-Hx组肝功恢复相对较快,术后168h(7d)与SO-Hx组相比,差别已无显著性(p>0.05);OJ3-Hx组和OJ7-Hx组PCNA的标记指数和HGFmRNA的表达无论是峰值水平还是峰值后衰退的表达都较弱,与SO-Hx组相比,差别均有显著性(P<0.05);而OJ1-Hx组PCNA的标记指数和HGF mRNA的表达接近SO-Hx组,肝切除术后168h(7d),差别已无显著性(p>0.05)。
结论1.胆总管结扎诱导的梗阻性黄疸动物模型,能较好的模拟肝门部胆管癌梗阻性黄疸的一些病理生理特点,重复性及稳定性好;2.胆道梗阻导致的高胆红素血症明显抑制肝切除术后的肝再生,抑制程度与梗阻时间和黄疸水平相关,梗阻时间越长,黄疸水平越高,抑制作用表现越强;3.术前梗阻时间短、胆红素处于较低水平,才可能相对安全地行肝切除术。
Objective To approach the effect of different degrees of obstructive jaundice on the post-hepatectomy of rats liver regeneration., and provide a theoretical basis for clinical application.
Methods Spragure-Dawley rats model of obstructive jaundice was set up and used in measurement at different time points of the level of jaundice. Different groups were divided in accordance with the level of jaundice. 1. SO-Hx groups: normal rat partial hepatectomy groups, 2. OJ1-Hx groups: one days on obstructive jaundice of rat partial hepatectomy groups. 3. OJ3-Hx groups: three days on obstructive jaundice of rat partial hepatectomy guoups.4. OJ7-Hx groups: seven days on obstructive jaundice of rat partial hepatectomy groups; After the operation, the rat mortality, the ratio of residual liver weight / body weight, serum liver function, immunohistological analysis of PCNA index and semiquantitative RT-PCR to determine the HGF mRNA expression in liver tissues were observed.
Results After biliary obstruction was induced by common bile duct ligation,serum total bilirubin of SD rats was elevated to the peak (about 85 times) of jaundice at 168 hours of biliary obstruction, and then slow decline. The mortality rate of partial hepatectomy rats were increased after biliary obstruction . The mortality rates of one days on obstructive jaundice, three days on obstructive jaundice, seven days on obstructive jaundice were 6.67%, 26.67%, 46.67% and significantly higher than the control group(0%).The ratio of the right lobe of the liver weight / body weight of the OJ3-Hx group and the OJ7-Hx group were significantly lower than the control group, and their difference were statistical significance(P<0.05).While the OJ1-Hx group was close to the control group, and their difference were not statistical significance(P>0.05).The post-hepatectomy liver function of OJ3-Hx group OJ7-Hx group slowly recovered, and the difference of OJ3-Hx group and OJ7-Hx group compared with the control group from 0 hour to 168 hours after hepatectomy were statistical significance(P<0.05). However, the liver function of OJ1-Hx group relatively smoothly recovered, and the difference of OJ1-Hx group compared with the control group at 168 hours of post-hepatectomy was not statistical significance(P>0.05). Both peak and peak deterioration of PCNA labeling index and HGF mRNA expression in liver tissues of OJ3-Hx group and OJ7-Hx group were weaker, and their difference of OJ3-Hx group and OJ7-Hx group compared with the control group were statistical significant (P <0.05).However , PCNA labeling index and HGF mRNA expression in liver tissues of OJ1-Hx group was close to the control group ,and their difference at 168 hours of post-hepatectomy was not statistical significance(P>0.05). Conclusions 1.The obstructive jaundice rats model was induced by common bile duct ligation bile could simulate some pathophysiological features of obstructive jaundice of hilar cholangicarcinoma. The operation was reduplicative and stabile. 2.Hyperbilirubinemia caused by biliary obstruction obviously inhibited the post-hepatectomy liver regeneration. Inhibitory degree was related with obstructive time and the level of jaundice. And the inhibitory action was inhanced with prolonged obstructive time and elevated level of jaundice.3.Hepatectomy was considered relatively safe at a relatively low level of preoperative bilirubin and short time obstruction.
方法建立梗阻性黄疸SD大鼠模型,测定梗阻不同时相的黄疸水平,并根据黄疸不同水平分组:1.SO-Hx组:正常大鼠肝切除组,2.OJ1-Hx组:梗阻性黄疸1天肝切除组,3.OJ3-Hx组:梗阻性黄疸3天肝切除组,4.OJ7-Hx组:梗阻性黄疸7天肝切除组;观察肝切除术后动物死亡率、残肝重/体重的比值、生化检测术后肝功、免疫组化检测术后肝组织PCNA标记指数、RT-PCR检测肝组织HGF mRNA的表达情况。
结果胆总管结扎诱导的胆道梗阻SD大鼠血清总胆红素呈进行性升高,在梗阻168h(7d)达峰值(约85倍)后缓慢下降。胆道梗阻后行肝切除术后死亡率升高,OJ1-Hx组、OJ3-Hx组和OJ7-Hx组的死亡率分别为6.67%、26.67%和46.67%,明显高于对照组(0%);OJ3-Hx组和OJ7-Hx组肝切除术后168h(7d)的右叶肝重/体重比值明显低于SO-Hx组,差别有显著性(p<0.05),而OJ1-Hx组接近SO-Hx组,差别无显著性(p>0.05);OJ3-Hx组和OJ7-Hx组肝切除术后肝功恢复缓慢,术后0-168h与SO-Hx组相比,差别均有显著性(p<0.05);而OJ1-Hx组肝功恢复相对较快,术后168h(7d)与SO-Hx组相比,差别已无显著性(p>0.05);OJ3-Hx组和OJ7-Hx组PCNA的标记指数和HGFmRNA的表达无论是峰值水平还是峰值后衰退的表达都较弱,与SO-Hx组相比,差别均有显著性(P<0.05);而OJ1-Hx组PCNA的标记指数和HGF mRNA的表达接近SO-Hx组,肝切除术后168h(7d),差别已无显著性(p>0.05)。
结论1.胆总管结扎诱导的梗阻性黄疸动物模型,能较好的模拟肝门部胆管癌梗阻性黄疸的一些病理生理特点,重复性及稳定性好;2.胆道梗阻导致的高胆红素血症明显抑制肝切除术后的肝再生,抑制程度与梗阻时间和黄疸水平相关,梗阻时间越长,黄疸水平越高,抑制作用表现越强;3.术前梗阻时间短、胆红素处于较低水平,才可能相对安全地行肝切除术。
Objective To approach the effect of different degrees of obstructive jaundice on the post-hepatectomy of rats liver regeneration., and provide a theoretical basis for clinical application.
Methods Spragure-Dawley rats model of obstructive jaundice was set up and used in measurement at different time points of the level of jaundice. Different groups were divided in accordance with the level of jaundice. 1. SO-Hx groups: normal rat partial hepatectomy groups, 2. OJ1-Hx groups: one days on obstructive jaundice of rat partial hepatectomy groups. 3. OJ3-Hx groups: three days on obstructive jaundice of rat partial hepatectomy guoups.4. OJ7-Hx groups: seven days on obstructive jaundice of rat partial hepatectomy groups; After the operation, the rat mortality, the ratio of residual liver weight / body weight, serum liver function, immunohistological analysis of PCNA index and semiquantitative RT-PCR to determine the HGF mRNA expression in liver tissues were observed.
Results After biliary obstruction was induced by common bile duct ligation,serum total bilirubin of SD rats was elevated to the peak (about 85 times) of jaundice at 168 hours of biliary obstruction, and then slow decline. The mortality rate of partial hepatectomy rats were increased after biliary obstruction . The mortality rates of one days on obstructive jaundice, three days on obstructive jaundice, seven days on obstructive jaundice were 6.67%, 26.67%, 46.67% and significantly higher than the control group(0%).The ratio of the right lobe of the liver weight / body weight of the OJ3-Hx group and the OJ7-Hx group were significantly lower than the control group, and their difference were statistical significance(P<0.05).While the OJ1-Hx group was close to the control group, and their difference were not statistical significance(P>0.05).The post-hepatectomy liver function of OJ3-Hx group OJ7-Hx group slowly recovered, and the difference of OJ3-Hx group and OJ7-Hx group compared with the control group from 0 hour to 168 hours after hepatectomy were statistical significance(P<0.05). However, the liver function of OJ1-Hx group relatively smoothly recovered, and the difference of OJ1-Hx group compared with the control group at 168 hours of post-hepatectomy was not statistical significance(P>0.05). Both peak and peak deterioration of PCNA labeling index and HGF mRNA expression in liver tissues of OJ3-Hx group and OJ7-Hx group were weaker, and their difference of OJ3-Hx group and OJ7-Hx group compared with the control group were statistical significant (P <0.05).However , PCNA labeling index and HGF mRNA expression in liver tissues of OJ1-Hx group was close to the control group ,and their difference at 168 hours of post-hepatectomy was not statistical significance(P>0.05). Conclusions 1.The obstructive jaundice rats model was induced by common bile duct ligation bile could simulate some pathophysiological features of obstructive jaundice of hilar cholangicarcinoma. The operation was reduplicative and stabile. 2.Hyperbilirubinemia caused by biliary obstruction obviously inhibited the post-hepatectomy liver regeneration. Inhibitory degree was related with obstructive time and the level of jaundice. And the inhibitory action was inhanced with prolonged obstructive time and elevated level of jaundice.3.Hepatectomy was considered relatively safe at a relatively low level of preoperative bilirubin and short time obstruction.
引文
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