摘要
目的:观察特异性α1肾上腺素能受体拮抗剂哌唑嗪长期给药对四氯化碳(CCl4)所致大鼠肝纤维化(肝硬化)的影响。方法:48只雄性SD大鼠随机分为4组,模型对照组(M组)、哌唑嗪治疗组(P组)、哌唑嗪对照组(D组)和正常对照组(N组)。M组和P组动物通过给予40%CCl4棉籽油溶液3.0mL/kg体重每周2次皮下注射诱导肝纤维化,共12周。D组和N组接受等量的棉籽油皮下注射,用法及时间同M组和P组。自第5周开始P组和D组动物给予每日1次50μg/200g体重的哌唑嗪溶液灌胃,N组和M组同时给予等量蒸馏水灌胃,8周后处死动物,下腔静脉采血测定有关肝功能指标,门静脉插管测定门静脉压力,取肝组织HE染色观察病理组织学改变,VG染色在病理图文分析系统下测定肝组织内胶原纤维面积。结果:CCl4诱导12周后M组见明显肝纤维化及肝硬化,肝脏组成结构消失,假小叶形成。哌唑嗪治疗8周后P组肝硬化程度显著加重,包括肝脏病理学改变,血清γ球蛋白水平,门静脉压力[(240.6±31.2)mmH2Ovs(204.8±29.6)mmH2O,P<0.05]及肝组织胶原纤维面积百分比[(18.4±4.9)%vs(8.0±2.4)%,P<0.05]。哌唑嗪本身并不引起肝损害或增加CCl4的肝毒性,由生化检查发现P组丙氨酸氨基转移酶、天冬氨酸氨基转移酶、血清总蛋白、白蛋白和病理检查肝细胞坏死、脂肪变性与M组相比差异无显著性及D组无任何肝损害证实。结论:哌唑嗪长期给药加重CCl4诱导的大鼠肝纤维化(肝硬化)程度及门脉高压症。
Objective To investigate the effects of long-term administration of prazosin, a specific α1 adrenergic antagonist, on liver fibrosis （cirrhosis） induced by carbon tetrachloride （CC14） in rats. Methods Forty-eight SD rats were randomized to model-control groups （group M）, prazosin-therapy group （group P）, prazosin-control group （group D）, or normal control group （group N）. The rats in groups M and P were administered a mixed solution of 40% CC14 and cottonseed oil to induce liver fibrosis. 4 weeks after the model establishment, the rats in groups P and D received a gastric injection of prazosin while those in groups M and N received distilled water. Hepatic functions, portal venous pressure were detected, pathohistological changes in the hepatic tissues were observed, and area of intrahepatic collagen fibers was measured. Results Following 12-week induction of CC14, marked hepatic fibrosis and cirrhosis occurred in group M, with disappearance of normal hepatic structures and formation of pseudolobules. Cirrhosis worsened 8 weeks after prazosin treatment, including pathological changes, serum γ-globulin levels, portal venous pressure [ （240.6 ± 31.2） mmI-I20 vs （204.8 ± 29.6） mmH2O, P 〈 0.05 ], and area of collagen fibers [ （ 18.4 ± 4.9） % vs （8.0 ± 2.4） %, P 〈 0.05 ]. Prazosin itself did not cause hepatic damage or increase the hepatotoxicity of CCl4. It was confirmed that biological and pathological examinations did not differed significantly between group P and group M and no hepatic damage developed in group D. Conclusion Long-term administration of prazosin may aggravate CCl4-induced liver fibrosis and portal hypertension in rats.
出处
《实用医学杂志》
CAS
2008年第5期723-725,共3页
The Journal of Practical Medicine
关键词
肝硬化
哌唑嗪
四氯化碳
门静脉压
Liver cirrhosis Prazosin Carbon tetrachloride Portal pressure
