丹参对实验性大鼠腹膜纤维化病变的影响

目的：探讨丹参对实验性大鼠腹膜纤维化病变的影响和可能的作用机制。方法：采用4.25%含糖透析液＋脂多糖致腹膜纤维化模型。将大鼠随机分成3组：对照组、模型组、丹参组。模型组每日腹腔内直接注射4.25%含糖透析液20ml,丹参组每日腹腔内直接注射4.25%含糖透析液20ml和丹参粉剂1g/kg,两组都在第3、5、7天予脂多糖（LPS）0.6mg/kg体重腹腔注射;对照组每日腹腔注射生理盐水20ml。30d后行4h腹膜平衡试验,处死各组大鼠,检测腹膜功能;留取壁层腹膜组织做HE及Masson染色,并留取血液和腹透液做ELISA法测转化生长因子-β。结果：模型组与对照组、丹参组相比超滤量和D/D0Glu明显减少,D/Pcr明显增加;模型组与对照组、丹参组相比,壁层腹膜厚度明显增厚,新生小血管明显增多,TGF-β的浓度也明显升高;差异有统计学意义。结论：丹参能有效的防治腹膜纤维化的进程。     

雌二醇抗肝纤维化的实验性研究

目的 探讨雌二醇对大鼠肝纤维化的影响及机制,以便对肝纤维化的治疗提供一种新的途径。方法 CCL4诱导大鼠肝纤维化动物模型,观察雌二醇对大鼠肝纤维化形成过程中血清AST、ALT、HA、CIV,以及肝组织胶原纤维沉积的影响。结果 雌二醇降低AST、ALT,HA、CIV及肝组织胶原纤维组织的沉积（P〈0．05）。结论 雌二醇有抑制大鼠肝纤维化进展的作用。     

黄芪丹参有效组分及其配伍抗肾纤维化的体内研究进展

近年来,中医药防治慢性肾脏病的临床实践表明：肾纤维化的发病多以气虚为本,以血瘀为标,以气虚血瘀证为关键病机,即因气虚而发病,因血瘀而致疾病迁延难愈,虚与瘀贯穿于疾病过程的始终,不可分割。因此,“气虚”、“血瘀”证是肾纤维化的常见证候,补气药、活血药是防治肾纤维化的常用药物,而黄芪、丹参则是治疗慢性肾脏病中最常见的中药之一,笔者就近年黄芪、丹参有效组分及其配伍抗肾纤维化的实验研究作一综述。     

白花丹提取物对CCl4肝纤维化动物模型的影响

目的观察白花丹提取物与复方丹参滴丸对大鼠实验性肝纤维化的治疗效果,并进行比较。方法将40只SD大鼠随机分为空白对照组、模型对照组、白花丹组、复方丹参滴丸组。除空白对照组外,其余均用四氯化碳油剂皮下注射诱发大鼠肝纤维化,第8周处死动物,以测定血清谷丙氨酸转换酶、谷草氨基酸转换酶活性、透明质酸、层粘连蛋白、Ⅲ型前胶原、Ⅳ型胶原、总胆红素的含量作为指标观察白花丹提取物和复方丹参滴丸对慢性肝脏损害和抗肝纤维化的治疗作用。结果检测表明白花丹提取物和复方丹参滴丸均能不同程度降低血清中ALT、AST、TBIL、HA、LN、CIV、PCⅢ的含量,与模型组存在显著性差异（P〈0.05）。白花丹组与复方丹参滴丸组相比有统计学意义（P〈0.05）。结论复方丹参滴丸和白花丹提取物都有减轻大鼠实验性肝纤维化作用,增强实验性大鼠抵抗CCl4致慢性肝损伤能力和抗肝纤维化能力,其中白花丹提取物的作用更显著。     

重组人肝再生增强因子对实验性肝纤维化Ⅰ、Ⅲ型胶原基因表达的影响

目的　了解重组人肝再生增强因子对实验性肝纤维化Ⅰ、Ⅲ型胶原基因表达的影响。方法　建立CCl4中毒性及人血白蛋白免疫损伤性 2种大鼠肝纤维化模型 ,在造模的同时给予不同剂量的重组人肝再生增强因子 (hALR)。在不同的时间点留取大鼠肝组织标本 ,提取总RNA ,用逆转录 聚合酶链反应 (RT PCR)测定Ⅰ、Ⅲ型胶原的基因表达水平。结果　在两种模型中hALR低剂量组大鼠肝组织I型胶原 (CCl4模型 2、4、6、8周分别为 1 .71± 0 .2 6、3 .42± 0 .67、3 .76± 0 .43、3 .3 3± 0 .69;人血白蛋白模型尾静脉攻击中、攻击后分别为 3 .86± 0 .66、2 .98± 0 .40 ) ,Ⅲ型胶原(CCl4模型 2、4、6、8周分别为 0 .97± 0 .1 6、2 .0 3± 0 .3 2、1 .86± 0 .3 3、1 .66± 0 .2 3 ;人血白蛋白模型尾静脉攻击中、攻击后分别为 2 .63± 0 .3 4、2 .0 2± 0 .3 2 )的基因表达水平在模型形成的不同阶段均明显低于模型组 ;高剂量hALR组大鼠肝组织Ⅰ、Ⅲ型胶原的基因表达水平均明显低于低剂量组。结论　重组人肝再生增强因子可能有抑制大鼠实验性肝纤维化Ⅰ、Ⅲ型胶原基因表达的作用。     

复方三叶香茶菜抗大鼠肝纤维化的实验研究

目的 研究复方三叶香茶菜(三叶香茶菜、黄根、三七)的保肝抗肝纤维化作用及其机制.方法 运用腹腔注射四氯化碳致大鼠肝纤维化模型,观察复方三叶香茶菜对大鼠肝纤维化的影响.运用苏木素-伊红染色、Massion染色检测肝纤维化的变化,生化检测肝脏羟脯氨酸、血清丙氨酸氨基转移酶(ALT)及天冬氨酸转移酶(AST),免疫组织化学法观察α-平滑肌肌动蛋白(α-SMA)的表达,分别应用RT-PCR和Western blot法检测转化生长因子β1(TGF-β1)及结缔组织生长因子(CTGF)mRNA和蛋白质表达状况.结果 复方三叶香茶菜能显著改善四氯化碳诱导的肝纤维化损伤,肝组织羟脯氨酸含量显著降低,血清ALT和AST含量明显低于肝纤维化模型组,肝组织TGF-β1及CTGF的mRNA和蛋白质表达均明显下降.结论 复方三叶香茶菜能有效地抑制四氯化碳诱导的肝纤维大鼠的肝损伤及纤维化进程,其主要机制可能与复方三叶香茶菜显著抑TGF-β1和CTGF的表达有关.     

实验性肝纤维化金属蛋白酶组织抑制因子—1基因表达的动态 …

观察实验性肝纤维化过程中金属蛋白酶组织抑制因子－１基因表达的动态变化。方法 建立四氯化碳中毒性及人血白蛋白损伤性两种大鼠肝纤维化模型，采用逆转录定量ＰＣＲ方法，测定肝纤维经不同阶段ＴＩＭＰ１的基因表达水平。结果 正常大鼠肝组织可见ＴＩＭＰ１的基因表达。     

细胞因子网络与肝纤维化

肝纤维化是肝损伤后的修复机制,其发生和形成是一个多因素相互促进相互制约的结果。肝星形细胞的过度激活是肝纤维化的中心事件,最终导致大量细胞外基质的合成。细胞因子作为重要的影响因素,它们之间相互作用并形成网络,刺激或抑制肝纤维化的发生发展,与肝纤维化的关系密切。本文就与肝纤维化关系密切的及有望应用于肝纤维化治疗的细胞因子作一综述。     

肝络欣丸对酒精性肝纤维化动物肝功能和血清肝纤维化指标的影响

目的:研究肝络欣丸治疗肝纤维化(hepatic fibrosis HF)的效果及部分作用机制.方法:采用酒精诱导HF动物模型.68只大鼠随机分为6组:正常组,模型组,秋水仙碱阳性对照组(简称对照组)、肝络欣丸低、中、高剂量(剂量分别为2.5、5和10g/kg)治疗组.模型组和肝络欣丸治疗组造模4周后,模型组和正常组0.85%氯化钠灌胃,治疗组大鼠予肝络欣治疗,低、中、高剂量组(剂量分别为2.5、5和lOg/kg),灌胃,每日2次,对照组试验时用生理盐水配制成浓度为1.25mg/ml的混悬液使用.实验8周后结束,检测各组大鼠血清丙氨酸氨基转移酶(ALT),天冬氨酸转氨酶(AST),透明质酸(HA),层黏连蛋白(LN),Ⅳ型胶原(1V-C).结果:与正常组比较:模型组大鼠血清ALT、AST、HA、LN、Ⅳ-C水平明显升高(P<0.01);肝络欣丸低、中、高剂量治疗组与对照组均可降低血清ALT、AST水平与模型组比较均有统计学意义(P<0.01).肝络欣丸低、中、高剂量治疗组与对照组均可降低HA、LN、Ⅳ-C水平与模型组比较差异有统计学意义(P<0.01);肝络欣丸低剂量治疗组与模型组比较LN、HA变化无统计学意义(P>0.05).结论:肝络欣丸能有效改善酒精诱导的HF大鼠肝组织损伤程度,可以有效降低模型大鼠血清ALT、AST等酶学指标和HA、LN、Ⅳ-C肝纤维化指标的含量水平.其机制可能是通过保护肝细胞,减轻肝脏炎症,抑制星状细胞活化和胶原合成,减轻肝细胞纤维增生以及肝细胞脂肪样变,促进肝脏代谢和肝细胞再生来实现的.     

黄芪地龙汤对肾脏病患者血清一氧化氮的影响

目的探讨黄芪地龙汤对原发性肾小球疾病(PGD)患者血清NO的影响.方法将60例PGD按肾功能分A、B两组,A组又随机分A1、A2组.A1与B组用黄芪地龙汤加西医治疗,A2组单用西医治疗;用比色法测定三组病人血清NO浓度并结合血清肌酐(Scr)等临床指标分析.结果治疗前A组病人血清NO明显高于对照组,B组显著低于对照组;治疗后血清NO水平A1组显著降低,B组显著升高;各临床指标A1组与B组明显改善;B组治疗前后Scr与血清NO作相关分析呈负相关(r=-0.6115,P＜0.02,r=-0.6291,P＜0.01),1/Scr的平均降低值,A2组＞B、A1两组,1/Scr与病程作回归分析,其回归系数(b),A2＜A1与B组比较(P均＜0.001).结论黄芪地龙汤治疗PGD能促进病情恢复,延缓慢性肾衰竭的进展.可能通过调节血清NO而起作用.     

益活Ⅰ号逆转肝纤维化的实验研究

目的：观察中药益气活血Ⅰ号方（益活Ⅰ号）治疗四氯化碳肝硬化模型大鼠效果。方法：采用空白对照、肝硬化模型对照和肝硬化模型治疗三组相比，应用测定肝功能、光镜、电镜下观察做对比研究。结果：益活Ⅰ号对大鼠肝纤维化有显著的逆转作用（Ｐ＜０．０５和Ｐ＜０．０１）。结论：益活Ⅰ号对造模大鼠肝纤维化有显著的逆转作用并有促进肝细胞再生、肝功能显著好转的作用     

Natural History of Hepatitis C Virus-Related Liver Fibrosis After Renal Transplantation

The aim of our study was to assess hepatitis C virus (HCV) evolution and long-term liver histology outcome in anti-HCV(+)/RNA(+) renal transplant (RT) patients. A total of 51 anti-HCV(+)/RNA(+) RT patients underwent liver biopsies (LB) every 3-4 years after transplantation (two LBs, n = 51; three LBs, n = 42; four LBs, n = 9). The hypervariable region (HVR)-1 of the HCV genome from all patients was characterized over time. Overall, the rate of liver fibrosis progression was 0.09 +/- 0.03 Metavir units/year. We identified three groups of patients: those in whom liver fibrosis remained stable (n = 21), those with progressing liver fibrosis (n = 21) and those with a regression in liver fibrosis (n = 10). In the last two groups, the progression and the regression of liver fibrosis were gradual during follow-up. Ferritin levels and hepatosiderosis were significantly higher in fibrosers. Initial fibrosis stage and high diversification of the HVR-1 of HCV genome between transplantation and the first liver biopsy were independent factors associated with liver fibrosis regression. In conclusion, in the current study, more than 10 years after renal transplantation, HCV infection was not harmful upon liver histology in more than 50% of patients. The diversification of the HVR-1 might be used to predict liver fibrosis outcome.     

复方黄黛片对 Solt-Farber 原发性肝癌大鼠血管新生作用的影响

目的：研究复方黄黛片对 Solt-Farber 原发性肝癌大鼠血管新生作用的影响。方法：将 50 只 SD 大鼠随机分为正常组、模型组、复方黄黛片高剂量组、中剂量组及低剂量组,每组 10 只。采用 Solt-Farber 二步法对除正常组外各组大鼠进行原发性肝癌造模,高（280 mg/kg）、中（140 mg/kg）及低剂量组（70 mg/kg）大鼠同时灌胃给予相应剂量的复方黄黛片,正常组与模型组则给予等量生理盐水,连续灌胃 18 周。末次灌胃 12 h 后取血,分离血清,检测其中肝功能指标水平（ALT、AST 及 TBIL）。取血完成,取各组大鼠肝脏,平均分为 4 份,分别进行病理组织学观察,采用免疫荧光法检测 HIF-1α、 VEGF 及 VEGFR-2 的表达情况,计算其相对表达量并进行 4 组比较。结果：与模型组 [ALT,（163.74±16.45）IU/L ;AST,（331.24±31.35）IU/L ;TBIL,（86.11±8.51）IU/L] 比较,各组大鼠中血清肝功能指标均明显降低,其差异具有统计学意义（P<0.05）;各组指标分别为高剂量组 [ALT,（71.43±7.83）IU/L ;AST,（112.52±12.58）IU/L ;TBIL,（34.23±3.23）IU/L],中剂量组 [ALT,（105.32±10.13）IU/L ;AST,（223.52±36.58）IU/L ;TBIL,（42.93±4.02）IU/L],低剂量组 [ALT,（122.34±12.11）IU/L ;AST,（254.21±25.14）IU/L ;TBIL,（51.27±5.26）IU/L]。高剂量组、中剂量组及低剂量组大鼠肝组织均出现不同程度的癌变,癌细胞呈梁状排列,但癌变程度均不及模型组。与模型组（HIF-1α,14.23±1.28 ; VEGF,11.52±1.10 ;VEGFR-2,16.34±1.65）比较,各组大鼠肝组织 HIF-1α、VEGF 及 VEGFR-2 的阳性表达情况均明显减轻,且相对表达量均明显降低,其差异具有统计学意义（P<0.05）;各组指标分别为高剂量组（HIF-1α,3.92±0.29 ;VEGF,2.87±0.26 ;VEGFR-2,3.45±0.40）、中剂量组（HIF-1α,6.36±0.65 ;VEGF,5.34±0.51 ;VEGFR-2,5.87±0.60）及低剂量组（HIF-1α,8.53±0.81 ;VEGF,7.76±0.74 ;VEGFR-2,8.12±0.87）。结论：复方黄黛片用于 Solt-Farber 原发性肝癌大鼠,可有效改善肝功能,抑制 HIF-1α、VEGF 及 VEGFR-2 等血管新生相关蛋白的表达。     

Ascites in Hepatitis C Liver Transplant Recipients Frequently Occurs in the Absence of Advanced Fibrosis

Ascites after liver transplantation is uncommon (3–7%) but causes morbidity and mortality. Although hepatitis C (HCV), pretransplant ascites, encephalopathy and cold ischemia time have been identified as predictors, neither posttransplant renal function nor the severity of recurrent HCV (inflammatory grade; fibrosis stage) has been systematically assessed. Among 173 HCV transplants (1 January 1998 to 31 December 2002), 18 patients (10%) developed posttransplant ascites. Cox proportional hazards models identified recipient female gender (hazard ratio [HR]= 12.18; p = 0.0001), cold ischemia time (HR = 1.17 per incremental hour; p = 0.021) and posttransplant creatinine (Cr) (HR = 1.56 per incremental 1.0 mg/dL; p = 0.0052) as independent predictors. Ludwig–Batts inflammation grade (HR = 1.32; p = 0.36) and fibrosis stage (HR = 1.63; p = 0.12) were not significant predictors. The 18 recipients had 19 ascites episodes; 12/19 had fibrosis stage 0, 1 or 2 (10/12 with stage 0 or 1). All 12 lacked diagnostic parenchymal or vascular histopathology. Renal function at ascites diagnosis were similar for transplants with fibrosis stage 0, 1 or 2 versus 3 or 4 (1.8 ± 1.6 vs. 1.6 ± 0.6 mg/dL; Cr clearance 39.6 ± 15.6 vs. 39.3 ± 13.4 mL/min/1.73 m²). In conclusion, recipient female gender, cold ischemia time and poor posttransplant renal function were independent predictors of ascites after HCV liver transplantation. Two thirds of ascites episodes, however, occurred without significant fibrosis or histopathology.     

丹参防治小鼠肝纤维化性骨质疏松的作用研究

目的:探讨肝硬化与骨质疏松症的关系并观察丹参对肝硬化导致的骨丢失的防治作用.方法:40?l4花生油皮下注射5周致小鼠肝纤维化,丹参用药6周后测定小鼠右股骨的骨Ca2 量和其他骨微量元素以及骨羟脯胺酸的含量,并与秋水仙碱作对照.结果:单用CCl4小鼠呈现典型的慢性肝损伤后肝纤维化的改变,骨重量和骨钙总量及骨羟脯胺酸的含量明显减少,而丹参组有明显的护肝及对抗骨丢失作用,其作用与秋水仙碱相当.结论:肝硬化可导致小鼠骨质疏松症,丹参对其所引起的肝纤维化及骨丢失有一定预防作用.     

Effect of Methyl Palmitate on the Formation of Epidural Fibrosis in an Experimental Epidural Fibrosis Model

ABSTRACT

Aim: To investigate the effects of local and systemic administration of methyl palmitate on the formation of epidural fibrosis. Material and Methods: Twenty-eight rats were randomly divided into four equal groups (control, Spongostan, local methyl palmitate and orally methyl palmitate) and laminectomy was performed between T11 and L1 in all rats. Local methyl palmitate (300 mg/kg) was applied with Spongostan; methyl palmitate (300 mg/kg) was given orally three times per week on different days for a total period of 4 weeks. Four weeks later, the vertebral column from T9 to L3, including the paraspinal muscles and epidural scar tissue, was removed en bloc and epidural fibrosis and arachnoidal involvement was graded and evaluated histopathologically. Kruskal-Wallis and Pearson Chi-Square test were used for statistical analysis. A statistically significant p-value was determined as p < 0.05. Results: The grading of epidural fibrosis was lower at a statistically significant level in orally-administrated methyl palmitate groups compared to the control and spongostan groups (p < 0.05). Conclusion: The findings of this study show that oral methyl palmitate decreases the formation of epidural fibrosis and that this effect of methyl palmitate could be mediated by reducing the functions of inflammatory cells such as macrophages, neutrophils and fibroblasts, including anti-inflammatory and antioxidant effects.     

The Effects of Cyclooxygenase (COX)-2 Inhibition on Ischemia-Reperfusion Injury in Liver Transplantation

Purpose: Our objective was to evaluate whether COX-2 inhibition with FK3311, a selective cyclooxygenase (COX)-2 inhibitor, improves transplanted liver function. Methods: Inbred male Lewis rats weighing 200–260 g were used. The donor liver was perfused with cold University of Wisconsin (UW) solution and then stored in the same solution at 4°C for 18 hr. After the preservation period, orthotopic liver transplantation was performed. Animals were divided into three groups: the control group; the FK low-dose group (1 mg/kg FK3311 i.v. 20 min before reperfusion); and the FK high-dose group (3 mg/kg FK3311 i.v. 20 min before reperfusion). Survival rate, serum GOT and GPT levels, liver tissue blood flow, and serum thromboxane B₂ (TxB₂) levels were compared among groups. Results: Survival rate was significantly better (p <. 05) and serum GOT levels 30 min after reperfusion were significantly lower (p <. 05) in the FK high-dose group compared to the other two groups. Four hours after reperfusion, GPT levels and liver tissue flow were significantly (p <. 05) better in the FK high-dose group compared to the control. Both 30 min and 4 hr after reperfusion, serum TxB₂ levels were significantly lower in the FK high-dose group compared to the control (p <. 05). Conclusion: COX-2 activity results in deteriorated liver function after I/R injury associated with transplantation, and selective COX-2 inhibition improved liver graft function.