远端脾静脉—肝动脉分流术治疗肝硬化门脉高压症动物模型的实验研究
|
摘要
目的:探讨肝硬化门脉高压症动物模型建立远端脾静脉-肝动脉分流术后降低胃脾区静脉压力的效果及血流动力学变化过程,为该术式应用于临床治疗肝硬化门脉高压症患者的可行性提供理论基础和科学依据。
方法:1、45头健康广西巴马小型猪随机分为正常对照组和实验组。对照组15头,实验组30头。其中实验组分成A、B两组,每组各15头。2、实验组分别采用CCL_4腹腔注射和口服饲养两种方法构建肝硬化门脉高压症动物模型,分别于给药第6、8、10、12、16、20周采集血标本检测肝功能等各项相关生化代谢指标,获取模型构建过程中的相关资料。3、已成模的肝硬化门脉高压症动物模型建立远端脾静脉-肝动脉分流术,观察血管吻合后胃脾区静脉血入肝的降压效果及门脉主干压力改变情况,经脾静脉注射亚甲蓝观察肝脏染色情况,获取相关实验资料。4、术后饲养实验猪,分别于术后第3天、1周及2周采集血标本,了解术后肝功能等各项相关指标的变化情况。5、术后4周时处死实验猪,处死前采集血样本检测各项相关生化代谢指标数据,切取小块肝组织及脾脏组织行常规病理检查,重新测量胃脾区及门脉主干静脉压力。6、所有数据处理均采用SPSS 13.0统计软件包分析完成。
结果:1、实验组A组和B组分别于给药第10周和20周成功构建肝硬化门脉高压症模型。实验证明腹腔注射法优于口服饲养法。
2、实验A、B组两组成模率分别为100%和80%。两组成模后的肝功能、肝脏病理分级、门静脉压力均达到实验设计要求。
3、肝硬化门脉高压症动物模型成模时门脉主干压力为29.90±2.73cmH_2O,脾静脉压力31.90±2.68cmH_2O,与正常对照组相比,差异有统计学意义(P＜0.05)。建立远端脾静脉-肝动脉吻合分流术后门脉主干压力23.49±1.10cmH_2O,脾静脉压力35.45±2.88cmH_2O,与成模时比较,差异有统计学意义(P＜0.05)。术后4周动物处死前门脉主干压力21.53±1.26cmH_2O,脾静脉压力23.09±1.36cmH_2O,与成模时和血管吻合后比较,差异有统计学意义(P＜0.05)。
4、建立远端脾静脉-肝动脉吻合分流术后,处于高压状态的胃脾区静脉血经血管吻合通道顺利进入肝脏,经脾静脉注射亚甲蓝观察肝脏染色良好,而腹腔其他脏器和血管系统并未见染色。说明高压状态的胃脾区静脉血入肝后降压效果良好。维持稳定降压效果的脾静脉压力为23.09±1.36cmH_2O,术后4周动物处死前离断肝动脉后肝动脉残余压力为13.55±0.84cmH_2O与建立分流术后的脾静脉形成的压力差为9.55±1.32cmH_2O。
5、此术式建立后到术后4周动物处死前肝硬化病理改善不明显,但无因缺氧缺血引起的肝坏死发生,脾脏淤血肿大消失。
6、术后4周动物处死前肝功能与正常对照组相比差异有统计学意义(P＜0.05),与成模时比较有所改善。术后不同时期的血气、凝血功能指标、血氨等指标与正常对照组和成模时相比差异均有统计学意义(P＜0.05)。
结论:1、CCL_4腹腔注射法及口服饲养法均能够成功构建肝硬化门脉高压症动物模型,实验证明腹腔注射法优于口服饲喂法,前者造模周期短,成模率高,动物死亡率低,成模后动物手术打击耐受性好,是一种理想的造模方法。2、远端脾静脉-肝动脉分流术能够有效降低肝硬化门脉高压症动物模型的门脉主干压力和胃脾区静脉压力,胃脾区静脉血分流入肝的最适脾静脉压力是23.09±1.36cmH_2O,压力差为9.55±1.32cmH_2O,两者是维持稳定降压效果的原始动力。3、远端脾静脉-肝动脉分流术后对肝硬化门脉高压症动物模型的肝功能、电解质、凝血功能、血氨、动脉血气在术后一周内的影响最大,术后2周后随着肝硬化程度的减轻而逐渐恢复,术后4周恢复到成模时状态。4、建立远端脾静脉-肝动脉分流术后动物模型脾脏的组织病理学表现明显改善,而肝脏的组织病理学改变不明显。
Objective: To approach the effects of distal splenic vein hepatic artery shunt in hepatic cirrhosis portal hypertension animal model. Providing the rationale and science basis for this technique's application in clinically treatting hepatic cirrhosis portal hypertension patients.
Methods: 1、40 health pigs(ba ma,guang xi) were randomly divided into two groups:normal control(n=10) and experimental group(n=30). The experimental group'pigs were randomly divided into two groups:Group A(n=15) and Group B (n=15).2、The experimental animals were used two methods(CCL_4 intraperitoneal injection and oral administration) to construct the hepatic cirrhosis portal hypertension animal model.Taking the correlate datas from this process.3、Establishing distal splenic vein hepatic artery shunt in animal model and observing the effects of stomach spleen region's venous pressure and portal vein's pressure.Injectting the methylene blue through splenic vein to observe staining in liver.Taking correlate experimental data.4、After the operation,we collect the samples to get the message of hepatic function'change in 3 days,1 week and 2 weeks.5.Before we execute the experiment animals in the 4 weeks,we collect samples , measure the splenic vein pressure and main portal vein(MPV) regularly.6.All data processing used SPSS 13.0 statistical package to analyze.
Result: 1.Group A:The time of success is 10 weeks and the rate of success is 100 percent.Group B:The time of success is 20 weeks and the rate of success is 80 percent.The experiment certificates that intraperitoneal injection outstrip oral administration.2.The portal hypertension(PHT) animal model'MPV pressure is 29.90±2.73cmH_2O and the splenic vein(SV) pressure is 31.90±2.68cmH_2O.To compare with the normal control ,the discrepancy has statistical significance(P <0.05, n=22).After operation,the MPV pressure is 23.49±1.10cmH_2O and the SV pressure is 35.45±2.88cmH_2O, Compared with prooperation'pressure, the discrepancy has statistical significance(P<0.05).Before the sacrifice of animal, theV pressure is 21.53±1.26cmH_2O and the SV pressure is 23.09±1.36cmH_2O, Compare MPd with prooperation'pressure, the discrepancy has statistical significance(P<0.05).3.After distal splenic vein hepatic artery shunt in hepatic cirrhosis portal hypertension animal model, the spleen venous blood can enter liver through vascular anastomosis way.Methylene blue is injected from the SV,and the liver'coloretur is fine.Other organs and vascular systems are not color.The effect of shunt is good.When the SV pressure is 23.09±1.36cmH_2O,it can keep stable effect of underpressure.The hepatic artery'residue pressure after mutilat the hepatic artery is 13.55±0.84cmH_2O.The dp is 9.55±1.32cmH_2O. 4.Compared with prooperation'patho,the amelioration is not obviously,but the hepatic function is better.
Conclusion: 1、The intraperitoneal injection method and oral administration both can success in constructting hepatic cirrhosis portal hypertension animal model,the experiment certificate that intraperitoneal injection outstrip oral administration.2、Distal splenic vein hepatic artery shunt can utility degrade MPV pressure SV pressure.The optimizate SV pressure is 23.09±1.36cmH_2O and the dp is 9.55±1.32cmH_2O.They are primitive motive of keepping underpressure stable.3、The effects of distal end splenic vein hepatic artery shunt in hepatic cirrhosis portal hypertension animal model with Hepatic function、dielectric、blood clotting、blood ammonia and arterial blood gas(ABG) are temple in 1 week after operation,they can recover gradually.The histopathology change of liver is not obviously,but the change of spleen is obviously.4、Our empirical study provid redundant rationale and science according for this shunt in hepatic cirrhosis portal hypertension patients.
方法:1、45头健康广西巴马小型猪随机分为正常对照组和实验组。对照组15头,实验组30头。其中实验组分成A、B两组,每组各15头。2、实验组分别采用CCL_4腹腔注射和口服饲养两种方法构建肝硬化门脉高压症动物模型,分别于给药第6、8、10、12、16、20周采集血标本检测肝功能等各项相关生化代谢指标,获取模型构建过程中的相关资料。3、已成模的肝硬化门脉高压症动物模型建立远端脾静脉-肝动脉分流术,观察血管吻合后胃脾区静脉血入肝的降压效果及门脉主干压力改变情况,经脾静脉注射亚甲蓝观察肝脏染色情况,获取相关实验资料。4、术后饲养实验猪,分别于术后第3天、1周及2周采集血标本,了解术后肝功能等各项相关指标的变化情况。5、术后4周时处死实验猪,处死前采集血样本检测各项相关生化代谢指标数据,切取小块肝组织及脾脏组织行常规病理检查,重新测量胃脾区及门脉主干静脉压力。6、所有数据处理均采用SPSS 13.0统计软件包分析完成。
结果:1、实验组A组和B组分别于给药第10周和20周成功构建肝硬化门脉高压症模型。实验证明腹腔注射法优于口服饲养法。
2、实验A、B组两组成模率分别为100%和80%。两组成模后的肝功能、肝脏病理分级、门静脉压力均达到实验设计要求。
3、肝硬化门脉高压症动物模型成模时门脉主干压力为29.90±2.73cmH_2O,脾静脉压力31.90±2.68cmH_2O,与正常对照组相比,差异有统计学意义(P＜0.05)。建立远端脾静脉-肝动脉吻合分流术后门脉主干压力23.49±1.10cmH_2O,脾静脉压力35.45±2.88cmH_2O,与成模时比较,差异有统计学意义(P＜0.05)。术后4周动物处死前门脉主干压力21.53±1.26cmH_2O,脾静脉压力23.09±1.36cmH_2O,与成模时和血管吻合后比较,差异有统计学意义(P＜0.05)。
4、建立远端脾静脉-肝动脉吻合分流术后,处于高压状态的胃脾区静脉血经血管吻合通道顺利进入肝脏,经脾静脉注射亚甲蓝观察肝脏染色良好,而腹腔其他脏器和血管系统并未见染色。说明高压状态的胃脾区静脉血入肝后降压效果良好。维持稳定降压效果的脾静脉压力为23.09±1.36cmH_2O,术后4周动物处死前离断肝动脉后肝动脉残余压力为13.55±0.84cmH_2O与建立分流术后的脾静脉形成的压力差为9.55±1.32cmH_2O。
5、此术式建立后到术后4周动物处死前肝硬化病理改善不明显,但无因缺氧缺血引起的肝坏死发生,脾脏淤血肿大消失。
6、术后4周动物处死前肝功能与正常对照组相比差异有统计学意义(P＜0.05),与成模时比较有所改善。术后不同时期的血气、凝血功能指标、血氨等指标与正常对照组和成模时相比差异均有统计学意义(P＜0.05)。
结论:1、CCL_4腹腔注射法及口服饲养法均能够成功构建肝硬化门脉高压症动物模型,实验证明腹腔注射法优于口服饲喂法,前者造模周期短,成模率高,动物死亡率低,成模后动物手术打击耐受性好,是一种理想的造模方法。2、远端脾静脉-肝动脉分流术能够有效降低肝硬化门脉高压症动物模型的门脉主干压力和胃脾区静脉压力,胃脾区静脉血分流入肝的最适脾静脉压力是23.09±1.36cmH_2O,压力差为9.55±1.32cmH_2O,两者是维持稳定降压效果的原始动力。3、远端脾静脉-肝动脉分流术后对肝硬化门脉高压症动物模型的肝功能、电解质、凝血功能、血氨、动脉血气在术后一周内的影响最大,术后2周后随着肝硬化程度的减轻而逐渐恢复,术后4周恢复到成模时状态。4、建立远端脾静脉-肝动脉分流术后动物模型脾脏的组织病理学表现明显改善,而肝脏的组织病理学改变不明显。
Objective: To approach the effects of distal splenic vein hepatic artery shunt in hepatic cirrhosis portal hypertension animal model. Providing the rationale and science basis for this technique's application in clinically treatting hepatic cirrhosis portal hypertension patients.
Methods: 1、40 health pigs(ba ma,guang xi) were randomly divided into two groups:normal control(n=10) and experimental group(n=30). The experimental group'pigs were randomly divided into two groups:Group A(n=15) and Group B (n=15).2、The experimental animals were used two methods(CCL_4 intraperitoneal injection and oral administration) to construct the hepatic cirrhosis portal hypertension animal model.Taking the correlate datas from this process.3、Establishing distal splenic vein hepatic artery shunt in animal model and observing the effects of stomach spleen region's venous pressure and portal vein's pressure.Injectting the methylene blue through splenic vein to observe staining in liver.Taking correlate experimental data.4、After the operation,we collect the samples to get the message of hepatic function'change in 3 days,1 week and 2 weeks.5.Before we execute the experiment animals in the 4 weeks,we collect samples , measure the splenic vein pressure and main portal vein(MPV) regularly.6.All data processing used SPSS 13.0 statistical package to analyze.
Result: 1.Group A:The time of success is 10 weeks and the rate of success is 100 percent.Group B:The time of success is 20 weeks and the rate of success is 80 percent.The experiment certificates that intraperitoneal injection outstrip oral administration.2.The portal hypertension(PHT) animal model'MPV pressure is 29.90±2.73cmH_2O and the splenic vein(SV) pressure is 31.90±2.68cmH_2O.To compare with the normal control ,the discrepancy has statistical significance(P <0.05, n=22).After operation,the MPV pressure is 23.49±1.10cmH_2O and the SV pressure is 35.45±2.88cmH_2O, Compared with prooperation'pressure, the discrepancy has statistical significance(P<0.05).Before the sacrifice of animal, theV pressure is 21.53±1.26cmH_2O and the SV pressure is 23.09±1.36cmH_2O, Compare MPd with prooperation'pressure, the discrepancy has statistical significance(P<0.05).3.After distal splenic vein hepatic artery shunt in hepatic cirrhosis portal hypertension animal model, the spleen venous blood can enter liver through vascular anastomosis way.Methylene blue is injected from the SV,and the liver'coloretur is fine.Other organs and vascular systems are not color.The effect of shunt is good.When the SV pressure is 23.09±1.36cmH_2O,it can keep stable effect of underpressure.The hepatic artery'residue pressure after mutilat the hepatic artery is 13.55±0.84cmH_2O.The dp is 9.55±1.32cmH_2O. 4.Compared with prooperation'patho,the amelioration is not obviously,but the hepatic function is better.
Conclusion: 1、The intraperitoneal injection method and oral administration both can success in constructting hepatic cirrhosis portal hypertension animal model,the experiment certificate that intraperitoneal injection outstrip oral administration.2、Distal splenic vein hepatic artery shunt can utility degrade MPV pressure SV pressure.The optimizate SV pressure is 23.09±1.36cmH_2O and the dp is 9.55±1.32cmH_2O.They are primitive motive of keepping underpressure stable.3、The effects of distal end splenic vein hepatic artery shunt in hepatic cirrhosis portal hypertension animal model with Hepatic function、dielectric、blood clotting、blood ammonia and arterial blood gas(ABG) are temple in 1 week after operation,they can recover gradually.The histopathology change of liver is not obviously,but the change of spleen is obviously.4、Our empirical study provid redundant rationale and science according for this shunt in hepatic cirrhosis portal hypertension patients.
引文
1 梁之祥,权启镇.门静脉高压症.济南:山东科学技术出社,2002.472-503.
2 区庆嘉,周修静,陈积圣,等.肝静脉阻断后循环代偿机制的探讨[J].中华实验外科杂志,1991,8(1):25-26.
3 吕明德,黄洁夫.腹腔注射CCL_4.配合营养控制制备犬肝硬化模型[J].中华实验外科杂志,1993,10(2):58-59.
4 马学惠.肝纤维化动物模型的造作方法[J].中华肝脏病杂志,1996,4(1):5.
5 周忠信,王捷,罗葆明.小型猪肝硬化模型建立过程中肝功能及组织病理学的改变[J].上海实验动物科学.2002.22(2):102-105.
6 Mclean E,Mclean AEM,Sutton PM.Instant cirrhosis,An improved methold for producing cirrhosis in rats by Simultaneous administration of CCL_4 and phenbarbitone[J].Br J Exp Pathol,1969,50:502.
7 吴孟超,杨广顺.大鼠肝硬变模型复制的研究[J].中华实验外科杂志.1984,1(4):45-48.
8 周炯亮.主编.化学性肝损害.第1版.北京:民卫生出版社,1989,12.
9 周丁华,应大君,肖凌云,等.大鼠肝硬变门脉高压症模型建立方法改进[J].中国普外基础与临床杂志,2000,7(1):22-24.
10 许洪伟,肝硬化患者门静脉系统血流动力学研究的临床价值[J].中华肝脏病杂志,2000,8:55.
11 鹿皎,崔建华,肝硬化患者门静脉脾静脉血流动力学多普勒检测及临床意义[J].徐州医学院学报.2005,25(3).
12 姜慧卿,张晓岚,秦玉彩.肝硬化患者门静脉系统血流动力学改变的彩色多普勒超声研究[J].胃肠病学和肝病学杂志,2001,10(4):343-345.
13 谭友文,於学军,殷玉梅.肝硬化门静脉高压门脉血流动力学检测及其临床意义[J].中华超声影像学杂志,200l,10(3):151-153.
14 Zhou X D.Clinical eralation of cryosargery in the treatment of primary liver cancer.Cancer,1988,61:1889.
15 张景,张庆富.肝脏微循环的研究进展[J].中国微循环,2007,(04):278-281.
16 Oda M,Yokomori H,Han JY.Regulatory mechanisms of hepatic Microcirculation[J].ClinHemorheolMicrocire,2003,29(3):167-82.
17 Hwang TL,Han ML,J.The changes of hepatic sinusoidal microcirculation and effects of nitric oxide synthase inhibiter during sepsis[J].Hepato-Gasterology,2003,50(49):213-216.
18 Nakata M,Nakamurak,Koda Y,et al.Alterations to hepatic microcirculation in thioacetamide-induced cirrhotic livers of rats[J].Osa-ka City Medical Journal,2002,48(1):1-8.
1 Saku M,Bocgceson B,Olin T,et al.An attempt to induce portal hypertension and esophageal varices in the rat[J].Eur Surg Res,1976,8(2):166-171
2 Dennis ML,Gustavo AM,Jorgc IF,et al.A reproducible caninc model of esophageal varices[J].Gastroenterology,1983,894(2):573-579
3 徐辉,陈虹彬,蒋明德等.合金支架治疗食管静脉曲张出血的实验研究[J]西南国防医药,2003,13(4):358-360
4 Stiegmann GV.Sun JH Hammond WS.Result of experimental endoscopic esophageal varix ligation[J].Am Surg,1988;54:105-108
5 Van Thiel DH,Gavaler JS,Skme FL,et al.Is feminieation in alcoholic men due in part to portal hypertension:a rat model[J].Gastroenterology.1980,78(1):81-91
6 李宗芳,刘效恭,王英等.缩窄门静脉主干1/2加丝线慢性栓塞术制备犬门静脉高压症模型[J].中华实验外科杂志,1997,14:314-315
7 李晓青 董蕾 罗金燕 不同静脉灌注量对门静脉高压失血性休克犬血流动力学的影响[J]中华肝脏病杂志,2002,10(5):374-377
8 Cametun CR,Karunaratne WAE.Carbon tetrschloride cirrhosis in relation to liver regeneration[J].J Path Bact,1936,42(1):1-21
9 吕明德,黄洁夫.腹腔注射四氯化碳配合营养控制制备犬肝硬化模型[J].中华实验外科杂志,1993,10:56-57
10 高萍,高伟,刘俊兰,李伟.正常犬在形成肝硬化后消化道病理改变及胃泌酸作用的影响[J].解放军医学杂志,2000,25(1):47-48
11 魏云巍张伟辉李勇薛东波.无创法监测犬肝硬化门静脉高压成模的应用[J]中华医学杂志,2004,84(7):599-60
12 刘小玲.经胃管胃肠灌注法建立稳定的犬肝硬化门脉高压模型的观察[J].局解手术学杂志,1994,3(4-12):29-30
13 周忠信,王捷,罗葆明.小型猪肝硬化模型建立过程中肝脏功能及组织病理学的改变[J].上海实验动物科学.2002,22(2):102-104
14 Zerm MA,Saber MA,Shafritz DA.Molecular mechanisms for changes in heptic protein synthesis induced by schistosomiasis infection in mice[J].Biochemistry,1985,84:36
15 曹罡,吉鸿,黎一鸣.门静脉系统用药制备犬肝硬化模型过程中肝储备功能的变化[J].中华实验外科杂志,2002,19(2):156-157
16 金树根.二甲基亚硝胺致实验性肝损伤的研究概况[J]中西医结合肝病杂志,1993,3(1):49-51
17 Madden JW,Gertman PM,Pcacock EE.Dimethylnitrosamine induce hepatic cirrhosis:a new canine model of an ancient human disease[J].Surgery,1970,68(1)260-267;disussion 267-268
18 Mwanza T,Miyamoto T.Okumura M,et al.Ultrasonography.biochemical and hematological profiles in liver disease caused by intravenous administration of dimethylnitrosamine in dogs[J].Jpn J Vet Res,1997,45(3):153-161
19 Shasha SM,Better OS,Chaimovitz C,et al.Haemodynamic studiesin dogs with chronic bile duct ligation[J].Clin Sci Mol Meal,1976,50(6):533-537
20 Bosch J,Enriquez R,Groszmann RJ,et al.Chronic bile duct ligation in the dog:hemodynamic characterization of a portal hypertensive model[J].Hepatology,1983,3(6):1002-1007
21 史留斌,彭承宏,彭淑牖等.原位辅助性部分肝移植治疗门静脉高压症的实验研究[J]中国危重病急救医学,2004,16(12):730-733
22 邓小荣 杨镇 裘法祖.门脉高压症猪脾组织中内皮素受体及诱导型一氧化氮合酶mRNA表达的意义[J]华中科技大学学报(医学版),2002,31(5):540-546
23 许光远,李大鹏,任大宏,杨镇.门脉高压症猪胃壁血管的内皮细胞损伤观察[J].毕中医学杂志,2001,25(5):247-248
24 潘峥 吴性江 李为苏等.犬肝硬化模型形成中肝功能性血流量的变化[J].中华实验外科杂志,2005,22(11):1405
25 杨卫平,蔡伟耀,邓侠兴等。胆汁性肝硬化犬门腔分流术后肝血液动力学变化[J]。上海第二医科大学学报,2004,20(4):296-298
26 Hellerbrand C,Stefanovic B,Giordano F,et al.The role of TGFbetal in initiating hepatic stellate cell activation in vivo[J].J Hepatol,1999,30(1):77-87
27 Buetgener FA,Gutierrez OH,Logadon GA.Angiographic,hetnodynamic and hitologic evahoation of portal hypertension and porportal fibrosis induced in the dog by intraportal polyvinyl alcohol injections[J].Radiology,1982,143(3):379-385
2 区庆嘉,周修静,陈积圣,等.肝静脉阻断后循环代偿机制的探讨[J].中华实验外科杂志,1991,8(1):25-26.
3 吕明德,黄洁夫.腹腔注射CCL_4.配合营养控制制备犬肝硬化模型[J].中华实验外科杂志,1993,10(2):58-59.
4 马学惠.肝纤维化动物模型的造作方法[J].中华肝脏病杂志,1996,4(1):5.
5 周忠信,王捷,罗葆明.小型猪肝硬化模型建立过程中肝功能及组织病理学的改变[J].上海实验动物科学.2002.22(2):102-105.
6 Mclean E,Mclean AEM,Sutton PM.Instant cirrhosis,An improved methold for producing cirrhosis in rats by Simultaneous administration of CCL_4 and phenbarbitone[J].Br J Exp Pathol,1969,50:502.
7 吴孟超,杨广顺.大鼠肝硬变模型复制的研究[J].中华实验外科杂志.1984,1(4):45-48.
8 周炯亮.主编.化学性肝损害.第1版.北京:民卫生出版社,1989,12.
9 周丁华,应大君,肖凌云,等.大鼠肝硬变门脉高压症模型建立方法改进[J].中国普外基础与临床杂志,2000,7(1):22-24.
10 许洪伟,肝硬化患者门静脉系统血流动力学研究的临床价值[J].中华肝脏病杂志,2000,8:55.
11 鹿皎,崔建华,肝硬化患者门静脉脾静脉血流动力学多普勒检测及临床意义[J].徐州医学院学报.2005,25(3).
12 姜慧卿,张晓岚,秦玉彩.肝硬化患者门静脉系统血流动力学改变的彩色多普勒超声研究[J].胃肠病学和肝病学杂志,2001,10(4):343-345.
13 谭友文,於学军,殷玉梅.肝硬化门静脉高压门脉血流动力学检测及其临床意义[J].中华超声影像学杂志,200l,10(3):151-153.
14 Zhou X D.Clinical eralation of cryosargery in the treatment of primary liver cancer.Cancer,1988,61:1889.
15 张景,张庆富.肝脏微循环的研究进展[J].中国微循环,2007,(04):278-281.
16 Oda M,Yokomori H,Han JY.Regulatory mechanisms of hepatic Microcirculation[J].ClinHemorheolMicrocire,2003,29(3):167-82.
17 Hwang TL,Han ML,J.The changes of hepatic sinusoidal microcirculation and effects of nitric oxide synthase inhibiter during sepsis[J].Hepato-Gasterology,2003,50(49):213-216.
18 Nakata M,Nakamurak,Koda Y,et al.Alterations to hepatic microcirculation in thioacetamide-induced cirrhotic livers of rats[J].Osa-ka City Medical Journal,2002,48(1):1-8.
1 Saku M,Bocgceson B,Olin T,et al.An attempt to induce portal hypertension and esophageal varices in the rat[J].Eur Surg Res,1976,8(2):166-171
2 Dennis ML,Gustavo AM,Jorgc IF,et al.A reproducible caninc model of esophageal varices[J].Gastroenterology,1983,894(2):573-579
3 徐辉,陈虹彬,蒋明德等.合金支架治疗食管静脉曲张出血的实验研究[J]西南国防医药,2003,13(4):358-360
4 Stiegmann GV.Sun JH Hammond WS.Result of experimental endoscopic esophageal varix ligation[J].Am Surg,1988;54:105-108
5 Van Thiel DH,Gavaler JS,Skme FL,et al.Is feminieation in alcoholic men due in part to portal hypertension:a rat model[J].Gastroenterology.1980,78(1):81-91
6 李宗芳,刘效恭,王英等.缩窄门静脉主干1/2加丝线慢性栓塞术制备犬门静脉高压症模型[J].中华实验外科杂志,1997,14:314-315
7 李晓青 董蕾 罗金燕 不同静脉灌注量对门静脉高压失血性休克犬血流动力学的影响[J]中华肝脏病杂志,2002,10(5):374-377
8 Cametun CR,Karunaratne WAE.Carbon tetrschloride cirrhosis in relation to liver regeneration[J].J Path Bact,1936,42(1):1-21
9 吕明德,黄洁夫.腹腔注射四氯化碳配合营养控制制备犬肝硬化模型[J].中华实验外科杂志,1993,10:56-57
10 高萍,高伟,刘俊兰,李伟.正常犬在形成肝硬化后消化道病理改变及胃泌酸作用的影响[J].解放军医学杂志,2000,25(1):47-48
11 魏云巍张伟辉李勇薛东波.无创法监测犬肝硬化门静脉高压成模的应用[J]中华医学杂志,2004,84(7):599-60
12 刘小玲.经胃管胃肠灌注法建立稳定的犬肝硬化门脉高压模型的观察[J].局解手术学杂志,1994,3(4-12):29-30
13 周忠信,王捷,罗葆明.小型猪肝硬化模型建立过程中肝脏功能及组织病理学的改变[J].上海实验动物科学.2002,22(2):102-104
14 Zerm MA,Saber MA,Shafritz DA.Molecular mechanisms for changes in heptic protein synthesis induced by schistosomiasis infection in mice[J].Biochemistry,1985,84:36
15 曹罡,吉鸿,黎一鸣.门静脉系统用药制备犬肝硬化模型过程中肝储备功能的变化[J].中华实验外科杂志,2002,19(2):156-157
16 金树根.二甲基亚硝胺致实验性肝损伤的研究概况[J]中西医结合肝病杂志,1993,3(1):49-51
17 Madden JW,Gertman PM,Pcacock EE.Dimethylnitrosamine induce hepatic cirrhosis:a new canine model of an ancient human disease[J].Surgery,1970,68(1)260-267;disussion 267-268
18 Mwanza T,Miyamoto T.Okumura M,et al.Ultrasonography.biochemical and hematological profiles in liver disease caused by intravenous administration of dimethylnitrosamine in dogs[J].Jpn J Vet Res,1997,45(3):153-161
19 Shasha SM,Better OS,Chaimovitz C,et al.Haemodynamic studiesin dogs with chronic bile duct ligation[J].Clin Sci Mol Meal,1976,50(6):533-537
20 Bosch J,Enriquez R,Groszmann RJ,et al.Chronic bile duct ligation in the dog:hemodynamic characterization of a portal hypertensive model[J].Hepatology,1983,3(6):1002-1007
21 史留斌,彭承宏,彭淑牖等.原位辅助性部分肝移植治疗门静脉高压症的实验研究[J]中国危重病急救医学,2004,16(12):730-733
22 邓小荣 杨镇 裘法祖.门脉高压症猪脾组织中内皮素受体及诱导型一氧化氮合酶mRNA表达的意义[J]华中科技大学学报(医学版),2002,31(5):540-546
23 许光远,李大鹏,任大宏,杨镇.门脉高压症猪胃壁血管的内皮细胞损伤观察[J].毕中医学杂志,2001,25(5):247-248
24 潘峥 吴性江 李为苏等.犬肝硬化模型形成中肝功能性血流量的变化[J].中华实验外科杂志,2005,22(11):1405
25 杨卫平,蔡伟耀,邓侠兴等。胆汁性肝硬化犬门腔分流术后肝血液动力学变化[J]。上海第二医科大学学报,2004,20(4):296-298
26 Hellerbrand C,Stefanovic B,Giordano F,et al.The role of TGFbetal in initiating hepatic stellate cell activation in vivo[J].J Hepatol,1999,30(1):77-87
27 Buetgener FA,Gutierrez OH,Logadon GA.Angiographic,hetnodynamic and hitologic evahoation of portal hypertension and porportal fibrosis induced in the dog by intraportal polyvinyl alcohol injections[J].Radiology,1982,143(3):379-385