Effects of chelerythine on hepatic pathology and hydroxyproline level in rats with CCl4-induced hepatic fibrosis
1
Citation
0
Reference
20
Related Paper
Citation Trend
Abstract:
Objective To observe the antifibrotic effects of chelerythine in rats with CCl4-induced hepatic fibrosis.Methods Hepatic fibrosis models in rats were established by injection of tetrachloride,in combination with the control of nutrition and the drinking 10% of alcohol.Four weeks later,chelerythine and γ-interferon were used in two groups respectively,for comparison to control and fibrotic model group.At the end of eight weeks,the histological changes and hydroxyproline content were detected.Result The pathological fibrosis scores and liver hydroxyproline content in rats with chelerythine or γ-interferon intervention decreased significantly as compared with fibrotic model group(P0.01),and the effect of chelerythine was found to be in a dose-dependent manner.Conclusions Chelerythine can improve the hepatic injuries in rats with tetrachloride-induced hepatic fibrosis.Keywords:
Hydroxyproline
CCL4
Hepatic fibrosis
Rat model
Tetrachloride
Cite
To investigate the effect of emodin on the development of hepatic fibrosis in rats.Forty percent of carbon tetrachloride (CCl4) dissolved in olive oil was injected subcutaneously to rats twice a week, for 6 weeks to produce hepatic fibrosis model, the rats of treated group were simultaneously injected with CCl4, treated with emodin in low, medium and high dose (20, 40 and 80 mg/kg body weight respectively) once a day for 42 days, which was dissolved in 0.5% sodium carboxymethylcellulose (CMC), while for rats of the control group, they only received CCl4 and CMC. Changes of serum hyaluronic acid, laminin and liver hydroxyproline were determined and histopathologic changes of liver was examined by optical microscopy and electronmicroscopy.Compared with the model group, in the emodin treated group: (1) Serum hyaluronic acid and laminin were markedly reduced (P < 0.05 or 0.01); (2) liver hydroxyproline was significantly decreased (P < 0.05 or 0.01); (3) degree of fibrosis was reduced (P < 0.05 or 0.01); (4) hepatocyte injury was ameliorated.Emodin has therapeutic effect on the development of hepatic fibrosis in rats. The effect might be related to slowing hepatocyte injury.
Hydroxyproline
CCL4
Hepatic fibrosis
Cite
Citations (5)
Objective To obsreve the effect of sanjiasanjiajianfang on Smad2/3 and tumor necrosis factor alpha(TNF-α) of hepatic tissue of hepatic fibrotic rats.Methods SD rats were classified into normal control group,model group,positive control group and touxietongluo group.Except the rats in the normal group,others were inflicted with liver fibrosis by intraperitoneal injection of 40% carbon tetrachloride,and were given medication at the same time.Rats were given colchicine 0.5 mg per kilogram everday in the positive control group,sanjiasanjiajianfang extractum 1.1 ml per 100 gram,normal saline 10 ml per kilogram everday in the normal group and the model group everday.After eight weeks,all the rats were excuted,and the hepatic tissues were kept for pathologic examination to observe hepatic fibrosis and immunohistochemical to detect Smad2/3 and TNF-α of hepatic tissue.Results Sanjiasanjiajianfang can relieve the pathological damage in hepatic tissues of hepatofibrosis rats and effectively reduce the expressive level of Smad2/3 and TNF-α,which was better than colchicine.Conclusion Sanjiasanjiajianfang can relieve the pathological damage in hepatic tissues of hepatofibrosis rats,and effectively reduce the expressive level of Smad2/3,TNF-α,so it can relieve of reverse hepatic fibrosis.
Colchicine
Hepatic fibrosis
Intraperitoneal injection
Hepatic stellate cell
Cite
Citations (0)
Hepatic fibrosis
CCL4
Hepatic stellate cell
Cite
Citations (1)
Hydroxyproline
Hepatic fibrosis
CCL4
Capsule
Hepatic stellate cell
Cite
Citations (4)
Objective To observe the curative effects of chelerythrine on the serum ALT and HA level of CCl4-induced hepatic fibrosis in rats.Methods Models of hepatic fibrosis were established by hypodermic injection of tetrachloride,in combination with the control of nutrition and the drinking of 10% alcohol to rats.According to histological sections,hepatic fibrosis in rats emerged at the end of the fourth week.Subsequently different doses of chelerythrine was used to treat hepatic fibrosis in rats.In addition,normal control group,fibrotic model group,γ-interfom group in experiment was arranged.At the end of the eighth week of treatment,serum hyaluronic acid level,alanine aminotransferase of all the rats were detected.Results Compared with fibrotic model group,all chelerythrine groups could decreased significantly the serum HA level of hepatic fibrosis in rats induced by CCL4(P0.01),which was not obviously distinguished from γ-interfom group(P0.05),while the serum ALT level of hepatic fibrosis in rats was not obviously different among all chelerythrine groups,IFN-γ group and fibrotic model group.Conclusions Chelerythrine can reduce the serum HA level of hepatic fibrosis,and the anti-fibrotic effects of chelerythine are identical with IFN-γ.But chelerythine could not improve the serum ALT level and protect live cell of hepatic fibrosis in rats.
Hepatic fibrosis
Chelerythrine
CCL4
Hepatic stellate cell
Cite
Citations (1)
Objective To explore the effect of angiotensin Ⅱ receptor blocker losartan on rats hepatic fibrosis induced by carbon tetrachloride(CCL4).Methods Hepatic fibrosis was induced in rats by intraperitoneal injection of carbon tetrachloride(40%).Meanwhile,losartan was given to the fibrosis+losartan intervention group rats(daily gavage),and sterile saline was given to the control rats for 6 weeks.Blood and liver tissue samples were taken for detecting aspartate aminotransferase(AST) and alanine aminotransferase(ALT).The pathological changes and fibrosis extent of liver tissues were observed by light microscope and polarizing microscope respectively.Collagen type I and collagen type Ⅲ were detected by immunohistochemistry.Liver AngⅡ and AT1R mRNA expressions were determined by RT-PCR.Results Compared with those of the model group,liver inflammation and hepatic fibrosis were significantly reduced in the fibrosis+losartan intervention group;collagen type I and collagen type Ⅲ content were lowered in the fibrosis+losartan intervention group(P0.05);the liver function was improved significantly.Meanwhile,the levels of AngⅡand AT1R mRNA in liver tissues also decreased(P0.05).Conclusion Losartan may has a therapeutic effect on carbon tetrachloride-induced liver fibrosis rats by reducing the expressions of liver AngⅡand AT1R.
Hepatic fibrosis
Intraperitoneal injection
CCL4
Cite
Citations (0)
Objective: The traditional Chinese medicine Anluohuaxianwan (ALHXW) has been used to treat liver fibrosis induced by chronic hepatitis B virus (HBV) infection. However, the anti-fibrosis mechanisms of ALHXW remain to be investigated. This study used a rat model of carbon tetrachloride (CCl(4))-induced liver fibrosis to explore the potential antifibrogenic mechanisms of ALHXW. Methods: Twenty-seven male Wistar rats were randomly assigned to control group, model group, and treatment group (n = 9 per group). Rats in the model and treatment group were injected intraperitoneally with 40% CCl(4)(2 ml/kg), and rats in the control group were administered saline twice a week for 6 weeks. Starting at week 4 following model construction, rats in the treatment group received daily gavages with ALHXW solution (concentration 0.15 g/ml) daily, while rats in the control and model groups were given saline for a total of 6 weeks. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured from blood samples collected at the end of weeks 3, 6 and 9. Histopathological examination of liver tissue was performed to evaluate liver fibrosis at week 9. At the same time, the mRNA expression of TGF-β1 and Smads in liver tissues was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR), and TGF-β1 protein level in the liver was measured by Western blot. Inter-group comparison was performed using analysis of variance (ANOVA) when the continuous data were normally distributed and satisfied the homogeneity of variance; otherwise, nonparametric tests were used. Categorical data were compared between groups using nonparametric tests. Results: ALHXW markedly alleviated liver injury in the treatment group after 3 weeks of therapy as indicated by a significantly reduced level of ALT compared with the model group [(162.98 ± 73.14)U/L vs (322.52 ± 131.76)U/L, P = 0.047], and a 39.8% reduction in AST level compared with the model group[ (537.56 ± 306.06)U/L vs (892.98 ± 358.19)U/L, P = 0.053]. Moreover, at the end of the 6-week therapy, histopathological diagnosis showed that liver fibrosis was significantly reduced in the ALHXW-treated group compared with that in the model group (P = 0.002). The relative expression of TGF-β1 mRNA and protein in the liver were significantly lower in ALHXW-treated rats than that in model rats (1.34 ± 0.31 vs 1.78 ± 0.45, P = 0.025; 0.39 ± 0.02 vs 0.57 ± 0.04, P = 0.003). Conclusion: ALHXW treatment can reverse CCl(4)-induced liver fibrosis in rats. Its mechanisms of anti-fibrosis may occur through the inhibition of TGF-β1 synthesis and TGF-β1/Smads signaling pathway, which in turn suppress the activation of hepatic stellate cells and thereby reverses fibrosis.目的： 中成药安络化纤丸已应用于临床治疗慢性乙型肝炎导致的肝纤维化，但其逆转肝纤维化的机制未明确。本研究利用四氯化碳（CCl(4)）诱导的大鼠肝纤维化模型，探索安络化纤丸抗纤维化的可能机制。 方法： 27只雄性wistar大鼠随机分为对照组、模型组和治疗组（n = 9），其中模型组和治疗组大鼠腹腔注射40% CCl(4) 2 ml/kg、对照组大鼠腹腔注射等渗盐水，每周2次、共6周。从建模第4周开始，治疗组大鼠每日灌胃安络化纤丸溶液（浓度为0.15 g/ml），其他两组大鼠灌胃等渗盐水，共6周。治疗3周和6周取血检测丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）。治疗6周结束后，取大鼠肝组织进行病理组织学评价，同时用荧光定量PCR法检测肝组织转化生长因子β1（TGFβ1）和Smads基因mRNA表达水平，用蛋白印迹法检测TGFβ1蛋白表达水平。计量资料是正态分布且满足方差齐性检验，多组间比较采用单因素方差分析；否则多组间比较采用非参数检验。等级资料多组间比较，采用非参数检验。 结果： 安络化纤丸治疗3周后，肝细胞损害减轻，治疗组大鼠ALT水平较模型组显著降低，（162.98±73.14）U/L对比（322.52±131.76）U/L，P = 0.047；AST水平较模型组下降39.8%，（537.56±306.06）U/L对比（892.98±358.19）U/L，P = 0.053。安络化纤丸治疗6周后，治疗组大鼠肝纤维化程度较模型组有显著改善（P = 0.002）。治疗组大鼠TGFβ1基因mRNA和蛋白相对表达水平显著低于模型组（1.34±0.31对比1.78±0.45，P = 0.025；0.39±0.02对比0.57±0.04，P = 0.003），差异均有统计学意义。 结论： 安络化纤丸能够逆转CCl(4)诱导的大鼠肝纤维化，其作用机制可能通过影响TGFβ1产生，从而抑制肝星状细胞激活而发挥抗肝纤维化作用。.
CCL4
Hepatic fibrosis
Cite
Citations (7)
Objective:In order to evaluate the curative effect and explore the possible mechanism of FFHQKL on anti-hepatic fibrosis.Methods:The rats was given intraperitoneal injection of porcine serum twice a week to establish the model of experimental immuno-damaged hepatic fibrosis. By using HE staining and special staining, the dynamical changes of hepatic histology of rats were observed to determine the curative effect of FFHQKL. By using immunohistochemical method, the dynamic changes in expression of MMP-13, TIMP-1 were determined in liver tissues from the experimental rats.Results:Compared with the control group, in which rats with hepatic fibrosis were not treated with FFHQKL, the histological examination of rat livers in the treatment groups showed that the total scores of hepatic fibrosis in treatment groups with high and low dosage were significantly decreased 2,3 months after the treatment(P0.01). With the decreased degree of liver fibrosis, the expression of TIMP-1 was significantly decreased and the expression of MMP-13 was significantly increased 2,3 months after the treatment in the high and low dosage groups of FFHQKL(P0.05 or P0.01).Conclusion:[WTBZ] FFHQKL could increase the expression of MMP-13,down-regulate the expression of TIMP-1, accelerate the degradation of ECM and reverse liver fibrosis.
Hepatic fibrosis
Intraperitoneal injection
Histology
Cite
Citations (0)
AIM:To induce hepatic fibrosis in rats by CCL4 and TAA respectively to compare the advantages and disadvantages of both methods.METHODS:Sixty male Sprague-Dawly rats were randomly divided into four groups.Hepatic fibrosis was induced in the ways introduced in references.Control groups were set respectively.The animals were sacrificed on day 28 and 56 after weighed.Serum was collected to examine the level of ALT,AST,HA and CIV and livers were homogenized to examine the level of SOD and MDA.The liver inflammation and collagen deposition were observed with HE and Masson's collagen stains and analyzed with scoring and staging systems.RESULTS:On day 28,significant differences in observed indexes were found between control and model groups,but no difference was seen between the 2 model groups.On day 56,significant differences was observed between the two model groups.CONCLUSION:The animal model of hepatic fibrosis induced by CCL4 is more suitable for researches on the mechanism of spontaneous regression of hepatic fibrosis and related strategies for treatment.The animal model of hepatic fibrosis induced by TAA is more suitable for researches on the mechanism of liver fibrosis,evaluation of antifibrotic effects of medicine,and evaluation of reliability of serous markers for the diagnosis of liver fibrosis.
Hepatic fibrosis
CCL4
Animal model
Rat model
Cite
Citations (1)
Objective:To observe prophylactic effect of curcumin on rat hepatic fibrosis induced by tetrachloride.Methods:Rat models of hepatic fibrosis were constructed by intraperitoneally injection of tetrachloride.Curcumin of 20 mg、10 mg、5 mg per 100 gram weight of rat were given to these rats respectively at the same time.Normal,fibrotic and positive groups were made as controls.After eight weeks,all rats were executed.Serum samples were kept for measuring serum levels of ALT、AST、HA、PC-Ⅲ、TGF-β、TNF-α.Left livers were extirpated for pathologic examination including H.E and Masson stainings.Grade of hepatic fibrosis were evaluate according to SSS system.Results:Serum levels of ALT、AST、HA、PC-Ⅲ、TGF-β、TNF-α of fibrotic group inceased significantly compared with that of normal group,and serum level of these iteme were depressed obviously in curcumin group(P0.05).Staining of H.E and Masson showed that degrees of hepatic fibrosis in curcumin groups were improved obviously compared with that of fibrotic group,and the scores of hepatic fibrosis in curcumin groups reduced significantly.Conclusion:Curcumin Can prevent rat hepatic fibrosis and improve hepatic functions,and Its effect is in dose-dependent.
Hepatic fibrosis
CCL4
Hepatic stellate cell
Cite
Citations (0)