活血利湿补益肝肾法治疗肝硬化的临床及实验研究
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摘要
背景:肝硬化是一种以肝组织弥漫性纤维化、假小叶和再生结节形成为特征的慢性肝病。引起肝硬化的病因很多,在我国以病毒性肝炎所致的肝硬化为主,西医认为发病机制主要是在肝脏多种细胞及细胞因子(cytokine,CK)参与下,引起细胞外基质(extracelluar matrix,ECM)的合成与降解失衡,即合成大于降解,导致ECM过度沉积所致。现已证实,肝星形细胞(hepatic stellate cell,HSC)是肝脏产生ECM的主要细胞,HSC活化是肝纤维化发生的中心环节。各种损肝因素导致肝损伤,继而引起肝细胞坏死及炎症刺激,相关细胞分泌多种CK激活HSC,产生大量的ECM。1995年,Sekelsky等在果蝇体内首先发现了Smads蛋白,随后的大量研究证实,Smads蛋白可将TGF-β信号直接由细胞膜激酶受体转导入细胞核内,是目前已知唯一的TGF-β受体(TβR)胞内激酶底物。现已证实,TGFβ-Smad信号转导过程可直接刺激HSC表型转化,诱导HSC凋亡,诱导基质基因表达,抑制基质降解,并且间接影响肝细胞、库普弗细胞、窦内皮细胞多项正常功能的发挥,起到促进肝纤维化发生发展的作用。慢性肝炎肝纤维化的发生率为59.36%,有25%～40%的肝纤维化患者发展成肝硬化,我国以乙型病毒性肝炎为多见。目前西医尚无有效的抗肝硬化的药物,中医药治疗慢性肝病历史悠久,作用明显。
目的:本课题以中医理论为指导,根据中医文献中有关“胁痛”“黄疸”“癥积”“臌胀”等的论述,认为肝硬化病位主要在肝脾,久则及肾,古代医家提出“阳虚易治,阴虚难调”,说明肝肾阴虚既是肝硬化失代偿期的一个重要病机,亦是常见而难治的证型。且该证型较其它证型更易引起肝昏迷和大出血等变证。结合现代医学对肝硬化的认识和临床实践体会,病机主要是湿热瘀毒互结,肝肾亏虚所致,确立活血利湿、补益肝肾的治疗大法,治疗采用的药物兰豆护肝颗粒是根据名老中医邹良材教授经验方兰豆枫楮汤研制而成,经临床多年应用观察,疗效确切。本课题临床研究部分方探讨了该方治疗肝硬化的疗效机理。实验研究部分探讨了兰豆护肝颗粒对大鼠肝纤维化的血清学、病理形态学影响,从而为防治肝纤维化的中药新药研究打下基础,并为临床早期诊治肝纤维化提供了依据。
方法:按照随机对照原则,本临床研究观察了180例肝炎肝硬化患者,对照组给予西医常规治疗,包括保肝降酶、利尿、退黄、补充白蛋白等基础措施;治疗组在西医一般治疗的基础上,运用兰豆护肝颗粒,主要组成药物有泽兰10g、路路通10g、黑料豆15g、楮实子20g、茵陈15g、牛膝10g、陈葫芦30g,每日3次,每次1包冲服,疗程均为6个月。观察指标包括临床症状体征、肝功能、肝纤指标等血清学检查及影像形态学改变。
实验研究运用现代实验技术方法,使用纯中药制剂兰豆护肝颗粒对实验性肝纤维化SD大鼠140只进行干预,方剂由泽兰10g、黑料豆10g、楮实子10g、路路通10g、川牛膝10g、茵陈10g、陈葫芦20g组成,制剂浓度为2.64g/ml。实验分为两个部分,分别为兰豆护肝颗粒的预防用药和治疗用药,选用秋水仙碱作为对照,应用血清生化学检查、常规病理学及免疫病理学检测等技术,观察了兰豆护肝颗粒预防、治疗肝纤维化的疗效,并探讨其作用机制。
结果:临床研究表明,兰豆护肝颗粒能够明显降低患者血清转氨酶活性,显著降低γ球蛋白,改善白/球比值,治疗前后两组临床症状体征、肝功能、肝纤指标等血清学检查及形态学均有不同程度改善,治疗后两组比较,疗效差异有统计学意义。治疗组基本治愈24例(27%),好转49例(54%),无效17例(19%),总有效率81.1%。对照组基本治愈19例(21%),好转34例(38%),无效37例(41%),总有效率58.9%。治疗组疗效优于对照组,两组比较经卡方检验,差异有统计学意义(P＜0.05)。同时兰豆护肝颗粒还可降低患者升高的HA、LN、Ⅳ型胶原,与治疗前比有差异有统计学意义(P＜0.05)。
实验研究结果表明:预防高剂量组、预防中剂量组、预防低剂量组、预防秋水仙碱组与模型Ⅰ组相比,ALT、AST差异有统计学意义(P＜0.05),余指标均有不同程度降低,但差异无统计学意义,兰豆护肝颗粒对大鼠急性肝损伤有一定的预防作用,并存在着一定的量效关系。对肝纤维化指标的影响,预防高剂量组、预防中剂量组、预防秋水仙碱组与正常组相比,除LN外,余无显著性差异,预防中剂量组、预防低剂量组纤维化指标均有不同程度的升高;与模型组相比,预防高剂量组、预防中剂量组、预防秋水仙碱组均有不同程度降低,HA(P＜0.01),PⅢNP(P＜0.05),差异有统计学意义,LN无明显差异;预防低剂量组HA(P＜0.01),差异有统计学意义,预防低剂量组LN、PⅢNP降低,但差异无统计学意义。
在治疗用药实验部分,治疗高剂量组、治疗中剂量组、治疗低剂量组、治疗秋水仙碱组各组肝功能均有恢复,与模型Ⅱ组相比无显著差异,CCl_4所致实验性大鼠肝损伤模型,停止CCl_4诱导后,肝功能可自我恢复,ALT、AST恢复较快,ALB、TP恢复较慢,大鼠肝脏修复功能比较强大,故各治疗组与模型组之间并差异无统计学意义。肝纤维化指标比较时,HA降低,与正常组比较无明显差异,与模型Ⅰ组比较差异显著(P＜0.01)、LN、PⅢNP较正常组显著升高(P＜0.05),与模型Ⅰ组比较无显著性差异,提示CCl_4诱导大鼠肝纤维化停止造模用药后有自我恢复状况,实验中模型Ⅱ组较模型Ⅰ组纤维化指标虽有所好转,但总体与正常组差异有统计学意义;治疗各组纤维化指标都有不同程度的降低,与模型Ⅱ组相比,治疗高剂量组、治疗中剂量组、治疗低剂量组、治疗秋水仙碱组各组纤维化指标均有改善,HA(P＜0.01),治疗高剂量组、治疗中剂量组、治疗秋水仙碱组各组LN(P＜0.05),治疗高剂量组、治疗秋水仙碱组PⅢNP(P＜0.05),差异有统计学意义,兰豆护肝颗粒对大鼠肝纤维化有较好的治疗作用,并存在着量效关系。病理形态学观察发现兰豆护肝颗粒对四氯化碳诱导的大鼠肝纤维化模型有较好的预防、治疗作用,能抑制Smad4的表达,减少ECM的沉积。
结论:兰豆护肝颗粒能缓解肝炎肝硬化患者的症状体征,保护肝功能,改善肝纤维化指标,实验研究表明兰豆护肝颗粒能显著改善大鼠CCl_4造模肝纤维化模型的肝功能、肝纤维化指标,可能与兰豆护肝颗粒能抑制Smad4的表达,减少ECM的沉积有关。
Purpose: From the theory of traditional Chinese medicine, we know that the postion of hepatical cirrhosis lies in the liver, spleen and kidney. Former doctors raise the gist of "it's easy to cure the yang-deficiency, while hard to yin-deficiency", it is reported that the syndrome of hepaticrenal yin-deficiency is an important pathogenesis, and also is a regular and stubborn syndrome, and this syndrome is easy to become hepaticalencephalopathy and bleeding than others. We are convinced of the pathogenesis of the hepatic cirrhosis is heat interwinding damp, and deficiency of liver and kidney. So activating the blood circulation and supplementing the liver and kidney is established. The compound drugs landou hugan granules is from the professor zouliangcai. After the clinical application, the effect is exact. The clinical part of this project is to declare the way of this compound to cure the hepatical cirrhosis, experimental part discuss the compound's effect on the hepatic fibrosis and morphologic pathology. And we can make the basis of treating hepatic cirrhosis.
Methods: Randomized controlled trial in accordance with the principles of clinical research of the 180 cases of hepatitis observed in patients with liver cirrhosis, the control group given conventional treatment of western medicine, including lowering the liver enzymes, diuretic, dispelling jaundice, supplementary measures such as albumin; treatment group in the general treatment of the basis of Western medicine , the use of Landou Hugan granules, a major component drugs Herba Lycopi , black bean, fructus broussonetiae, fructus liquidambaris, Cyathnla capitata Moq, herba artemisiae, Lagenaria vulgaris Ser, thick fried 100ml, morning and evening service hours, treated for 6 months. Observed clinical signs and symptoms, liver function, liver defibrase indicators serological examination and morphological changes of the image.
Experimental study on the use of modern experimental techniques, the use of pure Chinese medicine granules Landou Hugans on experimental hepatic fibrosis in 140 SD rats, prescription from Herba Lycopi , black bean, fructus broussonetiae, fructus liquidambaris, Cyathnla capitata Moq, herba artemisiae, Lagenaria vulgaris Ser, concentration of agents 2.64g/ml. Experiment is divided into two parts, namely, Landou hugan granules prevention and treatment of drug use, selection of colchicine as a control, application inspection serum biochemistry, pathology and immunopathology of conventional detection techniques, observation of the Landou Hugan granules prevention, treatment efficacy of hepatic fibrosis and to explore its mechanism.
Result: Clinical studies have shown that Landou Hugan granules can significantly reduced serum transaminase activity, a significant reduction inγ-globulin to improve the A/G ratio, the two groups before and after treatment, the clinical symptoms and signs, liver function, serum indicators of liver defibrase and morphological examination improvement in varying degrees, the two groups after treatment, the difference was statistically significant. Treatment group 24 cases of cure (27%), improvement in 49 cases (54%), ineffective in 17 patients (19%), total effective rate of 81.1%. The control group cured 19 patients (21%), improvement in 34 cases (38%), 37 cases of invalid (41%), the total effective rate 58.9%. Efficacy of the treatment group than the control group, two groups by chi-square test, the difference was statistically significant (P <0.05). Landou Hugan granules at the same time can reduce the increase in patients with HA, LN, IV collagen, and difference between the time of before and after treatment were statistically significant (P <0.05).
Experimental results show that: the prevention of high-dose group, middle dose group prevention, prevention of low-dose group, the prevention of colchicine group and model group I, ALT, AST were statistically significant differences (P <0.05), more than indicators are reduced to varying degrees, but the difference was not statistically significant, Landou Hugan granules in rats acute liver injury have some effect in prevention and there is a certain degree of dose-effect relationship. Indicators of the impact of liver fibrosis, prevention of high-dose group, middle dose group prevention, prevention colchicine group compared with the normal group, with the exception of LN, the more was no significant difference in the prevention of middle dose group, low-dose group to prevent fibrosis indicators increased in varying degrees; Compared with model group, the prevention of high-dose group, middle dose group prevention, prevention colchicine group were reduced to varying degrees, HA (P <0.01), PIIINP (P <0.05), There were significant differences, LN was no significant difference; the prevention of low-dose group of HA (P <0.01), the difference was statistically significant, the prevention of low-dose group LN, PIIINP lower, but the difference was not statistically significant.
Experimental drugs in the treatment of high-dose treatment groups, treatment dose, treatment of low-dose group, treatment colchicine group had restoration of liver function group, compared with model group II was no significant difference, CCl_4-induced experimental rat liver injury model, after the cessation of CCl_4-induced, self-restoration of liver function, ALT, AST to resume quickly, ALB, TP restoration of slow repair in rat liver was comparatively strong, so the treatment group and model group and the difference is not statistically significant. When compared to hepatic fibrosis, HA compared with the normal group had no significant differences in comparison with the model group I significantly different (P <0.01), LN, P III NP than the normal group was significantly higher (P <0.05), with the model group I no significant difference, suggesting that CCl_4-induced rat liver fibrosis model drug after cessation of self-recovery experiment in the model group than in model I II group, despite the improvement in fibrosis index, the overall difference with normal group statistics significance; the treatment of fibrotic markers in each group has a different degree of reduction compared with the model group II, the treatment of high-dose group, the treatment dose, treatment of low-dose group, the treatment of fibrosis colchicine group of indicators in each group were improvement, HA (P <0.01), treatment of high-dose group, the treatment dose group, treatment group colchicine group LN (P <0.05), treatment of high-dose group, treatment colchicine group P III NP (P <0.05), There were significant differences, Portland Hugan bean granules of rat liver fibrosis have a better therapeutic effect and dose-effect relationship exists. Observed that the pathomorphology of Landou Hugan granules on carbon tetrachloride-induced rat liver fibrosis model was better prevention, treatment effect, can inhibit the expression of Smad4 and reduce the deposition of ECM.
Conclusion: Landou Hugan granules can improve hepatitis symptoms in patients with liver cirrhosis, catabatic liver function and improve the liver fibrosis, experimental study of Landou Hugans can significantly improve liver function of the model CCM rat model of liver fibrosis, liver fibrosis indicators may be related to Landou Hugan granules inhibiting the expression of Smad4 and reduce the deposition of the ECM.
目的:本课题以中医理论为指导,根据中医文献中有关“胁痛”“黄疸”“癥积”“臌胀”等的论述,认为肝硬化病位主要在肝脾,久则及肾,古代医家提出“阳虚易治,阴虚难调”,说明肝肾阴虚既是肝硬化失代偿期的一个重要病机,亦是常见而难治的证型。且该证型较其它证型更易引起肝昏迷和大出血等变证。结合现代医学对肝硬化的认识和临床实践体会,病机主要是湿热瘀毒互结,肝肾亏虚所致,确立活血利湿、补益肝肾的治疗大法,治疗采用的药物兰豆护肝颗粒是根据名老中医邹良材教授经验方兰豆枫楮汤研制而成,经临床多年应用观察,疗效确切。本课题临床研究部分方探讨了该方治疗肝硬化的疗效机理。实验研究部分探讨了兰豆护肝颗粒对大鼠肝纤维化的血清学、病理形态学影响,从而为防治肝纤维化的中药新药研究打下基础,并为临床早期诊治肝纤维化提供了依据。
方法:按照随机对照原则,本临床研究观察了180例肝炎肝硬化患者,对照组给予西医常规治疗,包括保肝降酶、利尿、退黄、补充白蛋白等基础措施;治疗组在西医一般治疗的基础上,运用兰豆护肝颗粒,主要组成药物有泽兰10g、路路通10g、黑料豆15g、楮实子20g、茵陈15g、牛膝10g、陈葫芦30g,每日3次,每次1包冲服,疗程均为6个月。观察指标包括临床症状体征、肝功能、肝纤指标等血清学检查及影像形态学改变。
实验研究运用现代实验技术方法,使用纯中药制剂兰豆护肝颗粒对实验性肝纤维化SD大鼠140只进行干预,方剂由泽兰10g、黑料豆10g、楮实子10g、路路通10g、川牛膝10g、茵陈10g、陈葫芦20g组成,制剂浓度为2.64g/ml。实验分为两个部分,分别为兰豆护肝颗粒的预防用药和治疗用药,选用秋水仙碱作为对照,应用血清生化学检查、常规病理学及免疫病理学检测等技术,观察了兰豆护肝颗粒预防、治疗肝纤维化的疗效,并探讨其作用机制。
结果:临床研究表明,兰豆护肝颗粒能够明显降低患者血清转氨酶活性,显著降低γ球蛋白,改善白/球比值,治疗前后两组临床症状体征、肝功能、肝纤指标等血清学检查及形态学均有不同程度改善,治疗后两组比较,疗效差异有统计学意义。治疗组基本治愈24例(27%),好转49例(54%),无效17例(19%),总有效率81.1%。对照组基本治愈19例(21%),好转34例(38%),无效37例(41%),总有效率58.9%。治疗组疗效优于对照组,两组比较经卡方检验,差异有统计学意义(P＜0.05)。同时兰豆护肝颗粒还可降低患者升高的HA、LN、Ⅳ型胶原,与治疗前比有差异有统计学意义(P＜0.05)。
实验研究结果表明:预防高剂量组、预防中剂量组、预防低剂量组、预防秋水仙碱组与模型Ⅰ组相比,ALT、AST差异有统计学意义(P＜0.05),余指标均有不同程度降低,但差异无统计学意义,兰豆护肝颗粒对大鼠急性肝损伤有一定的预防作用,并存在着一定的量效关系。对肝纤维化指标的影响,预防高剂量组、预防中剂量组、预防秋水仙碱组与正常组相比,除LN外,余无显著性差异,预防中剂量组、预防低剂量组纤维化指标均有不同程度的升高;与模型组相比,预防高剂量组、预防中剂量组、预防秋水仙碱组均有不同程度降低,HA(P＜0.01),PⅢNP(P＜0.05),差异有统计学意义,LN无明显差异;预防低剂量组HA(P＜0.01),差异有统计学意义,预防低剂量组LN、PⅢNP降低,但差异无统计学意义。
在治疗用药实验部分,治疗高剂量组、治疗中剂量组、治疗低剂量组、治疗秋水仙碱组各组肝功能均有恢复,与模型Ⅱ组相比无显著差异,CCl_4所致实验性大鼠肝损伤模型,停止CCl_4诱导后,肝功能可自我恢复,ALT、AST恢复较快,ALB、TP恢复较慢,大鼠肝脏修复功能比较强大,故各治疗组与模型组之间并差异无统计学意义。肝纤维化指标比较时,HA降低,与正常组比较无明显差异,与模型Ⅰ组比较差异显著(P＜0.01)、LN、PⅢNP较正常组显著升高(P＜0.05),与模型Ⅰ组比较无显著性差异,提示CCl_4诱导大鼠肝纤维化停止造模用药后有自我恢复状况,实验中模型Ⅱ组较模型Ⅰ组纤维化指标虽有所好转,但总体与正常组差异有统计学意义;治疗各组纤维化指标都有不同程度的降低,与模型Ⅱ组相比,治疗高剂量组、治疗中剂量组、治疗低剂量组、治疗秋水仙碱组各组纤维化指标均有改善,HA(P＜0.01),治疗高剂量组、治疗中剂量组、治疗秋水仙碱组各组LN(P＜0.05),治疗高剂量组、治疗秋水仙碱组PⅢNP(P＜0.05),差异有统计学意义,兰豆护肝颗粒对大鼠肝纤维化有较好的治疗作用,并存在着量效关系。病理形态学观察发现兰豆护肝颗粒对四氯化碳诱导的大鼠肝纤维化模型有较好的预防、治疗作用,能抑制Smad4的表达,减少ECM的沉积。
结论:兰豆护肝颗粒能缓解肝炎肝硬化患者的症状体征,保护肝功能,改善肝纤维化指标,实验研究表明兰豆护肝颗粒能显著改善大鼠CCl_4造模肝纤维化模型的肝功能、肝纤维化指标,可能与兰豆护肝颗粒能抑制Smad4的表达,减少ECM的沉积有关。
Purpose: From the theory of traditional Chinese medicine, we know that the postion of hepatical cirrhosis lies in the liver, spleen and kidney. Former doctors raise the gist of "it's easy to cure the yang-deficiency, while hard to yin-deficiency", it is reported that the syndrome of hepaticrenal yin-deficiency is an important pathogenesis, and also is a regular and stubborn syndrome, and this syndrome is easy to become hepaticalencephalopathy and bleeding than others. We are convinced of the pathogenesis of the hepatic cirrhosis is heat interwinding damp, and deficiency of liver and kidney. So activating the blood circulation and supplementing the liver and kidney is established. The compound drugs landou hugan granules is from the professor zouliangcai. After the clinical application, the effect is exact. The clinical part of this project is to declare the way of this compound to cure the hepatical cirrhosis, experimental part discuss the compound's effect on the hepatic fibrosis and morphologic pathology. And we can make the basis of treating hepatic cirrhosis.
Methods: Randomized controlled trial in accordance with the principles of clinical research of the 180 cases of hepatitis observed in patients with liver cirrhosis, the control group given conventional treatment of western medicine, including lowering the liver enzymes, diuretic, dispelling jaundice, supplementary measures such as albumin; treatment group in the general treatment of the basis of Western medicine , the use of Landou Hugan granules, a major component drugs Herba Lycopi , black bean, fructus broussonetiae, fructus liquidambaris, Cyathnla capitata Moq, herba artemisiae, Lagenaria vulgaris Ser, thick fried 100ml, morning and evening service hours, treated for 6 months. Observed clinical signs and symptoms, liver function, liver defibrase indicators serological examination and morphological changes of the image.
Experimental study on the use of modern experimental techniques, the use of pure Chinese medicine granules Landou Hugans on experimental hepatic fibrosis in 140 SD rats, prescription from Herba Lycopi , black bean, fructus broussonetiae, fructus liquidambaris, Cyathnla capitata Moq, herba artemisiae, Lagenaria vulgaris Ser, concentration of agents 2.64g/ml. Experiment is divided into two parts, namely, Landou hugan granules prevention and treatment of drug use, selection of colchicine as a control, application inspection serum biochemistry, pathology and immunopathology of conventional detection techniques, observation of the Landou Hugan granules prevention, treatment efficacy of hepatic fibrosis and to explore its mechanism.
Result: Clinical studies have shown that Landou Hugan granules can significantly reduced serum transaminase activity, a significant reduction inγ-globulin to improve the A/G ratio, the two groups before and after treatment, the clinical symptoms and signs, liver function, serum indicators of liver defibrase and morphological examination improvement in varying degrees, the two groups after treatment, the difference was statistically significant. Treatment group 24 cases of cure (27%), improvement in 49 cases (54%), ineffective in 17 patients (19%), total effective rate of 81.1%. The control group cured 19 patients (21%), improvement in 34 cases (38%), 37 cases of invalid (41%), the total effective rate 58.9%. Efficacy of the treatment group than the control group, two groups by chi-square test, the difference was statistically significant (P <0.05). Landou Hugan granules at the same time can reduce the increase in patients with HA, LN, IV collagen, and difference between the time of before and after treatment were statistically significant (P <0.05).
Experimental results show that: the prevention of high-dose group, middle dose group prevention, prevention of low-dose group, the prevention of colchicine group and model group I, ALT, AST were statistically significant differences (P <0.05), more than indicators are reduced to varying degrees, but the difference was not statistically significant, Landou Hugan granules in rats acute liver injury have some effect in prevention and there is a certain degree of dose-effect relationship. Indicators of the impact of liver fibrosis, prevention of high-dose group, middle dose group prevention, prevention colchicine group compared with the normal group, with the exception of LN, the more was no significant difference in the prevention of middle dose group, low-dose group to prevent fibrosis indicators increased in varying degrees; Compared with model group, the prevention of high-dose group, middle dose group prevention, prevention colchicine group were reduced to varying degrees, HA (P <0.01), PIIINP (P <0.05), There were significant differences, LN was no significant difference; the prevention of low-dose group of HA (P <0.01), the difference was statistically significant, the prevention of low-dose group LN, PIIINP lower, but the difference was not statistically significant.
Experimental drugs in the treatment of high-dose treatment groups, treatment dose, treatment of low-dose group, treatment colchicine group had restoration of liver function group, compared with model group II was no significant difference, CCl_4-induced experimental rat liver injury model, after the cessation of CCl_4-induced, self-restoration of liver function, ALT, AST to resume quickly, ALB, TP restoration of slow repair in rat liver was comparatively strong, so the treatment group and model group and the difference is not statistically significant. When compared to hepatic fibrosis, HA compared with the normal group had no significant differences in comparison with the model group I significantly different (P <0.01), LN, P III NP than the normal group was significantly higher (P <0.05), with the model group I no significant difference, suggesting that CCl_4-induced rat liver fibrosis model drug after cessation of self-recovery experiment in the model group than in model I II group, despite the improvement in fibrosis index, the overall difference with normal group statistics significance; the treatment of fibrotic markers in each group has a different degree of reduction compared with the model group II, the treatment of high-dose group, the treatment dose, treatment of low-dose group, the treatment of fibrosis colchicine group of indicators in each group were improvement, HA (P <0.01), treatment of high-dose group, the treatment dose group, treatment group colchicine group LN (P <0.05), treatment of high-dose group, treatment colchicine group P III NP (P <0.05), There were significant differences, Portland Hugan bean granules of rat liver fibrosis have a better therapeutic effect and dose-effect relationship exists. Observed that the pathomorphology of Landou Hugan granules on carbon tetrachloride-induced rat liver fibrosis model was better prevention, treatment effect, can inhibit the expression of Smad4 and reduce the deposition of ECM.
Conclusion: Landou Hugan granules can improve hepatitis symptoms in patients with liver cirrhosis, catabatic liver function and improve the liver fibrosis, experimental study of Landou Hugans can significantly improve liver function of the model CCM rat model of liver fibrosis, liver fibrosis indicators may be related to Landou Hugan granules inhibiting the expression of Smad4 and reduce the deposition of the ECM.
引文
[1]刘冰.辨证论治肝硬化腹水80例[J].湖北中医杂志,2002,24(4):31.
[2]齐嫣,高爱芝.辨证论治肝硬化腹水102例[J].浙江中医杂志,2005,8(11):339.
[3]许院院,刘东江.辨证治疗肝硬化腹水50例[J].陕西中医,2005,26(1): 9-10.
[4]马异凡,王一林,康小玲.辨证治疗肝硬化腹水63例临床观察[J].湖南中医杂志,2004,20(1):15-16.
[5]杨红莉,同利香,郭小丽.软肝化瘀汤治疗肝硬化腹水58例[J].实用中西医结合临床,2005,5(2):13-14.
[6]段庆银.中药治疗肝硬化腹水155例临床观察[J].国医论坛,2002,17(6):22.
[7]李凌,应豪,陈汉诚.肝硬化的辨证施治[J].实用中医内科杂志,2005,19(2):123-125.
[8]沈龙柱,高虹,吴兆洪.辨病辨证治疗肝硬化腹水47例[J].辽宁中医药杂志,2004,31(6):473-474.
[9]张慧芳.辨证治疗失代偿期肝硬化100例总结[J].甘肃中医,2003,16(7):18-19.
[10]李纲.肝硬化临床证治探讨[J].光明中医,2003(6):61-62.
[11]段占全,段立峰.三七白术散为主治疗肝硬化腹水36例疗效观察[J].河北中医,2004,26(1):30.
[12]孟伟民,李宏斌.藏红花散治疗肝硬化51例[J].陕西中医,2005,26(1):12-13.
[13]史志宏.臌胀灵加减治疗肝硬化腹水50例[J].陕西中医,2005,26(1):11-12.
[14]王迎新,梁国英,刘朝霞.柔肝合剂为主治疗肝硬化的临床观察[J].中医药学报,2004,32(2):36-37.
[15]扈晓宇,陈云凤,王灵台.灵甲柔肝方治疗慢性乙型肝炎肝炎后肝硬化43例[J].中医研究,2005,18(6):28-30.
[16]陈立新.强复丸治疗肝炎后肝硬化176例[J].河南中医,2004,24(4):31-32.
[17]蔡敏,肖春玲,罗玫,等.比较两种脐敷疗法联合中药结肠透析对肝硬化难治性腹水诱发氮质血症的治疗效果[J].中西医结合肝病杂志,2004,14(2):81-82.
[18]孟光.回回蒜外敷治疗肝硬化腹水2例[J].四川中医,1997,15(6):33.
[19]陈帅.辨证分型敷脐治疗肝硬化腹水临床体会[J].江苏中医药,2003,24(11):19-20.
[20]鲁庆林.穴位贴敷为主治疗肝炎后肝硬化[J].中医外治杂志,1996(4):41.
[21]高南南,田泽,李玲玲,等.泽兰有效成分活血化瘀药理学的研究[J].中草药,1996,27(6):352-354.
[22]石宏志,高南南,李勇枝,等.泽兰有效部分L.F04对红细胞流变学的影响[J].航天医学与医学工程,2002,11(5):241-244.
[23]朱莉芬,杨尔和,李爱华,等.大豆提取物的药理研究[J].广东医学,1981,39(2):140-143.
[24]卫永第,陈荣杰.大豆总皂甙的部分药理作用[J].白求恩医科大学学报,1996,5(4):24-27.
[25]刘志刚,熊正英.大豆总皂甙对力竭运动大鼠一氧化氮(NO)及总一氧化氮合酶(TNOS)影响的实验研究[J].玉溪师范学院学报,2007,16(3):35-37.
[26]崔洪斌,陈近利,王蕊.大豆皂甙的生理活性及研究现状[J].解放军预防医学杂志,1998,11(2):147-149.
[27]李春,孙玉茹,孙有富.中药路路通化学成分的研究[J].药学学报,2002,14(4):243-245.
[28]鞠朝梁.路路通临床应用心得[J].云南中医中药杂志,1998,(S1):74-75.
[29]陈小川,王浦林,王晶晶.路路通配甲壳素镇痛与抗炎作用的研究及治疗类风湿性关节炎的疗效观察[J].四川中医,2003,12(6):43-45.
[30]熊玉兰,周钟鸣,王彦礼,等.茵陈有效成分对四氯化碳损伤的原代培养大鼠肝细胞的作用[J].中国实验方剂学杂志,2002,14(1):24-27.
[31]董岩,王新芳,崔长军,等.茵陈蒿的化学成分和药理作用研究进展[J].时珍国医国药,2008,22(4):57-59.
[32]沈飞海,葛文涛,潘竞锵,等.茵陈蒿提取物对胰岛素抵抗大鼠调脂降压作用及其机制研究[J].中药材,2007,(12):35-37.
[33]杨太成,赵树进,冼江,等.茵陈提取物的纯化及体外抗肿瘤作用[J].广东医学,2002,23(2):145-147.
[34]谢松强,纪忠岐.茵陈提取液对实验性动物肝损伤的作用[J].医药论坛杂志,2003,12(24):38-40.
[35]谢韬,梁敬钰,刘净.茵陈化学成分和药理作用研究进展[J].海峡药学,2004,6(1):65-67.
[36]韦倩,盖国忠,伊鹏菲,等.牛膝药理血清对血管内皮细胞影响的实验研究[J].长春中医药大学学报,2008,14(3):64-66.
[37]向道斌,葛家壁,李晓玉.牛膝多糖对小鼠体液免疫反应的增强作用[J].上海免疫学杂志,1994,9(3):52-53.
[38]蒋远明,刘颖菊.葫芦素B对大鼠肝内Fas及FasL表达的抑制作用.中药药理与临床,2000,16(3):1.
[1]梁扩寰,李绍白主编.肝脏病学[M].第2版.北京:人民卫生出版社.2003,821-822、849、1010-1011.
[2]夏启荣,何峰主编.肝硬化的诊断与治疗[M].第1版.北京:人民卫生出版社.2002,1、3、225.
[3]薛发轩.武汉地区8183例肝硬化患者分析.肝脏,2000,6:2-6.
[4]白宪光.546例肝炎后肝硬化患者的流行病学和临床特点.第四军医大学学报,2000,7:21-25.
[5]王悦.肝硬化失代偿期A-G型肝炎病毒感染的病原学调查.哈尔滨医科大学学报,1999,33:466.
[6]Zohrens G,Armbrust T,Meyer KH,etal.Interferon-α 2a increases serum Concentration of hyaluronic acid and typeⅢProcollagenaminoterminal ProPePtide in Patients with chronic hepatitis B virus infection.DigDisSci,1994:39:2007-2013.
[7]孔丽,李兵顺,任仲轩,等.IFN-α对慢性乙肝肝纤维化阻断作用的研究[J].临床肝胆病杂志,2006,13(6):57-59.
[8]牛俊奇,张清泉,余绳美,等.病毒性肝炎及肝硬化患者血浆PGE1和TXB2水平检测及临床意义[J].白求恩医科大学学报,1992,18(1):61-63.
[9]何文革,刘泽富,魏芳,等.前列腺素E1抗肝纤维化的临床疗效观察[J].临床内科杂志,2001,18(2):110-111.
[10]李良,朱化刚.前列腺素E1抑制血吸虫病家兔肝脏Ⅰ,Ⅲ型胶原生成的研究[J].中国普通外科杂志,2007,16(6):577-580.
[11]张成平.前列腺素E的生物学效应及在肝脏病理生理作用[J].国外医学.消化系疾病分册,1995,15(2):88-91.
[12]姜藻:尤大钰.16,16-二甲基前列腺素E2、秋水仙碱和硫酸锌抗肝纤维化的实验研究[J].中华消化杂志,1994,14(3):53-56.
[13]阳学风,曾明新,张明亮,等.马洛替酯抑制肝纤维化的实验与临床研究[J].世界华人消化杂志,1999,7(3):224-226.
[14]孟宪镛.肾上腺皮质激素治疗肝病的评价[J].临床肝胆病杂志,1989, 5(1):85-87.
[15]Kershenobich D,VargasF,Garcia-Tsao G.etal.Colchicine in the treatment of cirrhosis of the liver.N Engl J med,1988;318:1709-17.
[16]宋忠于,叶启发,明英姿,等.肝移植术后防治乙肝复发的策略[J].中国现代医学杂志,2006,16(6):918-922.
[17]刘建,吴国聪,张忠涛,等.Prevention and treatment of hepatitis B virus reinfection after livertransplantation[J].中华外科杂志,2005,43(15):976-979.
[18]冯众一,付维利,席力罡,等.小剂量乙肝免疫球蛋白(HBIG)联合拉米夫定(LAM)防治肝移植术后乙肝复发的应用研究[J].中华肝胆外科杂志,2006,12(12):857-858.
[19]王笑梅,兰孟东,段英,等.肝移植后乙型肝炎复发的临床表现与预后[J].胃肠病学和肝病杂志,2008,(1):55-58.
[20]徐雪勤.Clinical Significance of Detection of Blood Protein in Patients with Hepatocir-rhosis[J].中西医结合肝病杂志,2003,13(4):54-56.
[21]张卫卫,王学清,李岩.血清前白蛋白、胆碱酯酶对判断肝硬化患者肝储备功能及预后的临床价值[J].中国实用内科杂志,2002,5(11):130-132.
[22]冯金铭,胡日旺.肝炎后肝硬化生化指标变化与死因预后的关系[J].首都医药,2004,20:25-26.
[23]贾绮宾;吴改玲;梁学亚,等.肝硬化患者血中细胞因子及内毒素水平与肝功能及预后的关系[J].北京医学,2007,10(3):86-88.
[24]陈育霞.肝硬化自发性腹膜炎的临床分析[J].中国医疗前沿,2008,9(4):67-69.
[25]杜鹏辉,邓长生.肝硬化腹水的治疗现状与进展[J].医学新知杂志,2006,8(5):76-78.
[26]陈倩,张顺财,祝墡珠.肝硬化患者合并感染的回顾性研究[J].中国临床医学,2005,12(3):110-113.
[27]雷巧玲,姜慧玲,任爱萍.Prospective investigation of hospital infections in patients with liver cirrhosis[J].世界华人消化杂志,1998,12(11):97-99.
[28]范建高,王国良,曾民德.肝肾综合征研究进展[J].肝脏,1999,7(2):86-89.
[29]庹必光,晏永慧,史济经,等.HBV对失代偿期肝硬化预后的影响[J]中华肝脏病杂志,1998,14(2):55-47.
[30]钱林学,王宝恩.肝硬化预后因素和预后高危因素的研究[J]中华内科杂志,1995,9(5):87-89.
[1]刘秀英,胡怡秀,等.四氯化碳和猪血清肝纤维化模型组织病理比较.世界华人消化杂志,2004,12(8):1875-1879
[2]沈映君.中药药理学.北京:人民卫生出版社,2000:134
[3]马洪波,郎振为,等.慢性肝炎血液学检查与肝脏病理对照分析.临床荟萃,2001,16(18):822-824
[4]俞利平,陈小因,方志明.丹参注射液对大鼠酒精性肝损伤血清ALT,AST 的影响.中国中医基础医学杂志,2004,10(7):63
[5]梁扩寰,李绍白.肝脏病学.北京:人民卫生出版社,1995.208
[6]陈祝英,郑屏唐.慢性肝炎转氨酶与肝组织形态定量的关系.临床肝胆杂志,1998,14(1):47
[7]王英,贾杰.AST/ALT比值在各种肝病中的变化和意义.中国热带医学,2001,1(3):222
[8]Giannini E,Botta F,Fasoli A,et al.Progressive liver functional impairment 15 associated with an increase in AST、ALT ratio.Dig Dis Sci,1999,44:1249-1253.
[9]Bonacini M,Hadi C,Govindarajan S,et al.Utility of a discriminant score for diagnosing advanced fibrosis or cirrhosis in patients with chronic hepatitis C virus infection.Am J Gastroenterol.1997.92:1302-1304.
[10]宋育林,杨文卓,贾一滔,等.慢性肝病病理分级、分期与血清学指标关系的初步研究.胃肠病学,2001,6(2):78
[11]庞荣清,刘建昆,等.猕猴肝纤维化模型建立与评价.世界华人消化杂志,2005,13(16):1956
[12]Simeonora PP,Gallucci RM,Hulderman T,et al.The role of tumor necrosis factor-alpha in liver toxicity,inflammation and fibrosis induced by carbon tetrachloride.Toxicol Appl Pharmacol,2001,177(2):112-120.
[13]Rodriguez L,Cerbon AJ,Munoz ML.Effects of colchicines and colchiceine in a biochemical model of liver injury and fibrosis.Arch Med Res,1998,29(2):109-116.
[14]龚峻梅,朴英杰,陈素云,等急性CCl_((4))肝损伤的研究进展.国外医学#生理!病理科学与临床分册,2002,22(3)308-311.
[15]刘移民,周炯亮,杨杏芬,等几种亲肝毒物亚慢性实验中毒时肝纤维化过程的组织学.职业医学,1991,18(6):32-3251.
[16]王莹.现代职业医学.北京:人民卫生出版社,1999,336-338.
[17]宋健,钟惠闽,姚平,等.苦参素对实验性大鼠肝纤维化的防治作用.中国中西医结合消化杂志,2002,10(5):282-286.
[18]Jiang Z,You DY,Chen XC et al.Monitoring of serum markers for fibrosis during CCI4-induced liver damage.Effects of anti-fibrotic agents.J Hepatol.1992,16(3):282.
[19]程明亮,刘三都.肝纤维化的基础研究与临床.第1版.北京:人民卫生出版社,1996:246.
[20]De Caesteckr MP,Yabata T,Wang D.et al.The Smad4 activation domain(SAD)is a praline-rich,p300-dependent transcriptional activation domain.J Biol Chem,2000,275:2115.
[21]Liu C,Gaca MD,Swenson ES,et al.Smads 2 and 3 are differentially activated by transforming growth factor-beta(TGF-beta)in quies- cent and activated hepatic stellate cells.Constitutive nuclear local- ization of Smads in activated cells is TGF-beta-independent.J BiolChem,2003,278:11721-11728.
[22]Kitamura Y,Ninomiya H.Smad expression of hepatic stellate cells in liver cirrhosis in vivo and hepatic stellate cell line in vitro.Pathol Int,2003,53:18-26.
[23]梁志清,徐新宝,何振平.TGF-β受体及其信号转导分子smad4在大鼠纤维化肝脏的表达及意义.重庆医学,2002,31(7):546-547.
[24]Stroschein SL,Wang W,Luo K.Cooperative binding of Smad proteins to two adjacent DNA elements in the plasminogen activator inhibitor_promote mediates transforming growth factor beta_induced smad_dependen transcriptional activation.J Biol Chem,1999,274(14):9431-9441.
[25]徐新保,冷希圣,杨晓.反义Smad4基因转染对抗昆明小鼠肝脏纤维化发展的效果观察.中华普通外科杂志,2004,1(19):50-52.
[26]曾维政,吴晓玲,蒋明德。氧化苦参碱对肝纤维化大鼠Smad基因表达的影响世界华人消化杂志2005,13(8):984-987.
[2]齐嫣,高爱芝.辨证论治肝硬化腹水102例[J].浙江中医杂志,2005,8(11):339.
[3]许院院,刘东江.辨证治疗肝硬化腹水50例[J].陕西中医,2005,26(1): 9-10.
[4]马异凡,王一林,康小玲.辨证治疗肝硬化腹水63例临床观察[J].湖南中医杂志,2004,20(1):15-16.
[5]杨红莉,同利香,郭小丽.软肝化瘀汤治疗肝硬化腹水58例[J].实用中西医结合临床,2005,5(2):13-14.
[6]段庆银.中药治疗肝硬化腹水155例临床观察[J].国医论坛,2002,17(6):22.
[7]李凌,应豪,陈汉诚.肝硬化的辨证施治[J].实用中医内科杂志,2005,19(2):123-125.
[8]沈龙柱,高虹,吴兆洪.辨病辨证治疗肝硬化腹水47例[J].辽宁中医药杂志,2004,31(6):473-474.
[9]张慧芳.辨证治疗失代偿期肝硬化100例总结[J].甘肃中医,2003,16(7):18-19.
[10]李纲.肝硬化临床证治探讨[J].光明中医,2003(6):61-62.
[11]段占全,段立峰.三七白术散为主治疗肝硬化腹水36例疗效观察[J].河北中医,2004,26(1):30.
[12]孟伟民,李宏斌.藏红花散治疗肝硬化51例[J].陕西中医,2005,26(1):12-13.
[13]史志宏.臌胀灵加减治疗肝硬化腹水50例[J].陕西中医,2005,26(1):11-12.
[14]王迎新,梁国英,刘朝霞.柔肝合剂为主治疗肝硬化的临床观察[J].中医药学报,2004,32(2):36-37.
[15]扈晓宇,陈云凤,王灵台.灵甲柔肝方治疗慢性乙型肝炎肝炎后肝硬化43例[J].中医研究,2005,18(6):28-30.
[16]陈立新.强复丸治疗肝炎后肝硬化176例[J].河南中医,2004,24(4):31-32.
[17]蔡敏,肖春玲,罗玫,等.比较两种脐敷疗法联合中药结肠透析对肝硬化难治性腹水诱发氮质血症的治疗效果[J].中西医结合肝病杂志,2004,14(2):81-82.
[18]孟光.回回蒜外敷治疗肝硬化腹水2例[J].四川中医,1997,15(6):33.
[19]陈帅.辨证分型敷脐治疗肝硬化腹水临床体会[J].江苏中医药,2003,24(11):19-20.
[20]鲁庆林.穴位贴敷为主治疗肝炎后肝硬化[J].中医外治杂志,1996(4):41.
[21]高南南,田泽,李玲玲,等.泽兰有效成分活血化瘀药理学的研究[J].中草药,1996,27(6):352-354.
[22]石宏志,高南南,李勇枝,等.泽兰有效部分L.F04对红细胞流变学的影响[J].航天医学与医学工程,2002,11(5):241-244.
[23]朱莉芬,杨尔和,李爱华,等.大豆提取物的药理研究[J].广东医学,1981,39(2):140-143.
[24]卫永第,陈荣杰.大豆总皂甙的部分药理作用[J].白求恩医科大学学报,1996,5(4):24-27.
[25]刘志刚,熊正英.大豆总皂甙对力竭运动大鼠一氧化氮(NO)及总一氧化氮合酶(TNOS)影响的实验研究[J].玉溪师范学院学报,2007,16(3):35-37.
[26]崔洪斌,陈近利,王蕊.大豆皂甙的生理活性及研究现状[J].解放军预防医学杂志,1998,11(2):147-149.
[27]李春,孙玉茹,孙有富.中药路路通化学成分的研究[J].药学学报,2002,14(4):243-245.
[28]鞠朝梁.路路通临床应用心得[J].云南中医中药杂志,1998,(S1):74-75.
[29]陈小川,王浦林,王晶晶.路路通配甲壳素镇痛与抗炎作用的研究及治疗类风湿性关节炎的疗效观察[J].四川中医,2003,12(6):43-45.
[30]熊玉兰,周钟鸣,王彦礼,等.茵陈有效成分对四氯化碳损伤的原代培养大鼠肝细胞的作用[J].中国实验方剂学杂志,2002,14(1):24-27.
[31]董岩,王新芳,崔长军,等.茵陈蒿的化学成分和药理作用研究进展[J].时珍国医国药,2008,22(4):57-59.
[32]沈飞海,葛文涛,潘竞锵,等.茵陈蒿提取物对胰岛素抵抗大鼠调脂降压作用及其机制研究[J].中药材,2007,(12):35-37.
[33]杨太成,赵树进,冼江,等.茵陈提取物的纯化及体外抗肿瘤作用[J].广东医学,2002,23(2):145-147.
[34]谢松强,纪忠岐.茵陈提取液对实验性动物肝损伤的作用[J].医药论坛杂志,2003,12(24):38-40.
[35]谢韬,梁敬钰,刘净.茵陈化学成分和药理作用研究进展[J].海峡药学,2004,6(1):65-67.
[36]韦倩,盖国忠,伊鹏菲,等.牛膝药理血清对血管内皮细胞影响的实验研究[J].长春中医药大学学报,2008,14(3):64-66.
[37]向道斌,葛家壁,李晓玉.牛膝多糖对小鼠体液免疫反应的增强作用[J].上海免疫学杂志,1994,9(3):52-53.
[38]蒋远明,刘颖菊.葫芦素B对大鼠肝内Fas及FasL表达的抑制作用.中药药理与临床,2000,16(3):1.
[1]梁扩寰,李绍白主编.肝脏病学[M].第2版.北京:人民卫生出版社.2003,821-822、849、1010-1011.
[2]夏启荣,何峰主编.肝硬化的诊断与治疗[M].第1版.北京:人民卫生出版社.2002,1、3、225.
[3]薛发轩.武汉地区8183例肝硬化患者分析.肝脏,2000,6:2-6.
[4]白宪光.546例肝炎后肝硬化患者的流行病学和临床特点.第四军医大学学报,2000,7:21-25.
[5]王悦.肝硬化失代偿期A-G型肝炎病毒感染的病原学调查.哈尔滨医科大学学报,1999,33:466.
[6]Zohrens G,Armbrust T,Meyer KH,etal.Interferon-α 2a increases serum Concentration of hyaluronic acid and typeⅢProcollagenaminoterminal ProPePtide in Patients with chronic hepatitis B virus infection.DigDisSci,1994:39:2007-2013.
[7]孔丽,李兵顺,任仲轩,等.IFN-α对慢性乙肝肝纤维化阻断作用的研究[J].临床肝胆病杂志,2006,13(6):57-59.
[8]牛俊奇,张清泉,余绳美,等.病毒性肝炎及肝硬化患者血浆PGE1和TXB2水平检测及临床意义[J].白求恩医科大学学报,1992,18(1):61-63.
[9]何文革,刘泽富,魏芳,等.前列腺素E1抗肝纤维化的临床疗效观察[J].临床内科杂志,2001,18(2):110-111.
[10]李良,朱化刚.前列腺素E1抑制血吸虫病家兔肝脏Ⅰ,Ⅲ型胶原生成的研究[J].中国普通外科杂志,2007,16(6):577-580.
[11]张成平.前列腺素E的生物学效应及在肝脏病理生理作用[J].国外医学.消化系疾病分册,1995,15(2):88-91.
[12]姜藻:尤大钰.16,16-二甲基前列腺素E2、秋水仙碱和硫酸锌抗肝纤维化的实验研究[J].中华消化杂志,1994,14(3):53-56.
[13]阳学风,曾明新,张明亮,等.马洛替酯抑制肝纤维化的实验与临床研究[J].世界华人消化杂志,1999,7(3):224-226.
[14]孟宪镛.肾上腺皮质激素治疗肝病的评价[J].临床肝胆病杂志,1989, 5(1):85-87.
[15]Kershenobich D,VargasF,Garcia-Tsao G.etal.Colchicine in the treatment of cirrhosis of the liver.N Engl J med,1988;318:1709-17.
[16]宋忠于,叶启发,明英姿,等.肝移植术后防治乙肝复发的策略[J].中国现代医学杂志,2006,16(6):918-922.
[17]刘建,吴国聪,张忠涛,等.Prevention and treatment of hepatitis B virus reinfection after livertransplantation[J].中华外科杂志,2005,43(15):976-979.
[18]冯众一,付维利,席力罡,等.小剂量乙肝免疫球蛋白(HBIG)联合拉米夫定(LAM)防治肝移植术后乙肝复发的应用研究[J].中华肝胆外科杂志,2006,12(12):857-858.
[19]王笑梅,兰孟东,段英,等.肝移植后乙型肝炎复发的临床表现与预后[J].胃肠病学和肝病杂志,2008,(1):55-58.
[20]徐雪勤.Clinical Significance of Detection of Blood Protein in Patients with Hepatocir-rhosis[J].中西医结合肝病杂志,2003,13(4):54-56.
[21]张卫卫,王学清,李岩.血清前白蛋白、胆碱酯酶对判断肝硬化患者肝储备功能及预后的临床价值[J].中国实用内科杂志,2002,5(11):130-132.
[22]冯金铭,胡日旺.肝炎后肝硬化生化指标变化与死因预后的关系[J].首都医药,2004,20:25-26.
[23]贾绮宾;吴改玲;梁学亚,等.肝硬化患者血中细胞因子及内毒素水平与肝功能及预后的关系[J].北京医学,2007,10(3):86-88.
[24]陈育霞.肝硬化自发性腹膜炎的临床分析[J].中国医疗前沿,2008,9(4):67-69.
[25]杜鹏辉,邓长生.肝硬化腹水的治疗现状与进展[J].医学新知杂志,2006,8(5):76-78.
[26]陈倩,张顺财,祝墡珠.肝硬化患者合并感染的回顾性研究[J].中国临床医学,2005,12(3):110-113.
[27]雷巧玲,姜慧玲,任爱萍.Prospective investigation of hospital infections in patients with liver cirrhosis[J].世界华人消化杂志,1998,12(11):97-99.
[28]范建高,王国良,曾民德.肝肾综合征研究进展[J].肝脏,1999,7(2):86-89.
[29]庹必光,晏永慧,史济经,等.HBV对失代偿期肝硬化预后的影响[J]中华肝脏病杂志,1998,14(2):55-47.
[30]钱林学,王宝恩.肝硬化预后因素和预后高危因素的研究[J]中华内科杂志,1995,9(5):87-89.
[1]刘秀英,胡怡秀,等.四氯化碳和猪血清肝纤维化模型组织病理比较.世界华人消化杂志,2004,12(8):1875-1879
[2]沈映君.中药药理学.北京:人民卫生出版社,2000:134
[3]马洪波,郎振为,等.慢性肝炎血液学检查与肝脏病理对照分析.临床荟萃,2001,16(18):822-824
[4]俞利平,陈小因,方志明.丹参注射液对大鼠酒精性肝损伤血清ALT,AST 的影响.中国中医基础医学杂志,2004,10(7):63
[5]梁扩寰,李绍白.肝脏病学.北京:人民卫生出版社,1995.208
[6]陈祝英,郑屏唐.慢性肝炎转氨酶与肝组织形态定量的关系.临床肝胆杂志,1998,14(1):47
[7]王英,贾杰.AST/ALT比值在各种肝病中的变化和意义.中国热带医学,2001,1(3):222
[8]Giannini E,Botta F,Fasoli A,et al.Progressive liver functional impairment 15 associated with an increase in AST、ALT ratio.Dig Dis Sci,1999,44:1249-1253.
[9]Bonacini M,Hadi C,Govindarajan S,et al.Utility of a discriminant score for diagnosing advanced fibrosis or cirrhosis in patients with chronic hepatitis C virus infection.Am J Gastroenterol.1997.92:1302-1304.
[10]宋育林,杨文卓,贾一滔,等.慢性肝病病理分级、分期与血清学指标关系的初步研究.胃肠病学,2001,6(2):78
[11]庞荣清,刘建昆,等.猕猴肝纤维化模型建立与评价.世界华人消化杂志,2005,13(16):1956
[12]Simeonora PP,Gallucci RM,Hulderman T,et al.The role of tumor necrosis factor-alpha in liver toxicity,inflammation and fibrosis induced by carbon tetrachloride.Toxicol Appl Pharmacol,2001,177(2):112-120.
[13]Rodriguez L,Cerbon AJ,Munoz ML.Effects of colchicines and colchiceine in a biochemical model of liver injury and fibrosis.Arch Med Res,1998,29(2):109-116.
[14]龚峻梅,朴英杰,陈素云,等急性CCl_((4))肝损伤的研究进展.国外医学#生理!病理科学与临床分册,2002,22(3)308-311.
[15]刘移民,周炯亮,杨杏芬,等几种亲肝毒物亚慢性实验中毒时肝纤维化过程的组织学.职业医学,1991,18(6):32-3251.
[16]王莹.现代职业医学.北京:人民卫生出版社,1999,336-338.
[17]宋健,钟惠闽,姚平,等.苦参素对实验性大鼠肝纤维化的防治作用.中国中西医结合消化杂志,2002,10(5):282-286.
[18]Jiang Z,You DY,Chen XC et al.Monitoring of serum markers for fibrosis during CCI4-induced liver damage.Effects of anti-fibrotic agents.J Hepatol.1992,16(3):282.
[19]程明亮,刘三都.肝纤维化的基础研究与临床.第1版.北京:人民卫生出版社,1996:246.
[20]De Caesteckr MP,Yabata T,Wang D.et al.The Smad4 activation domain(SAD)is a praline-rich,p300-dependent transcriptional activation domain.J Biol Chem,2000,275:2115.
[21]Liu C,Gaca MD,Swenson ES,et al.Smads 2 and 3 are differentially activated by transforming growth factor-beta(TGF-beta)in quies- cent and activated hepatic stellate cells.Constitutive nuclear local- ization of Smads in activated cells is TGF-beta-independent.J BiolChem,2003,278:11721-11728.
[22]Kitamura Y,Ninomiya H.Smad expression of hepatic stellate cells in liver cirrhosis in vivo and hepatic stellate cell line in vitro.Pathol Int,2003,53:18-26.
[23]梁志清,徐新宝,何振平.TGF-β受体及其信号转导分子smad4在大鼠纤维化肝脏的表达及意义.重庆医学,2002,31(7):546-547.
[24]Stroschein SL,Wang W,Luo K.Cooperative binding of Smad proteins to two adjacent DNA elements in the plasminogen activator inhibitor_promote mediates transforming growth factor beta_induced smad_dependen transcriptional activation.J Biol Chem,1999,274(14):9431-9441.
[25]徐新保,冷希圣,杨晓.反义Smad4基因转染对抗昆明小鼠肝脏纤维化发展的效果观察.中华普通外科杂志,2004,1(19):50-52.
[26]曾维政,吴晓玲,蒋明德。氧化苦参碱对肝纤维化大鼠Smad基因表达的影响世界华人消化杂志2005,13(8):984-987.