乙肝转阴颗粒对化学性肝损伤和慢性肝纤维的保护作用及其机制研究
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摘要
目的:研究乙肝转阴颗粒(YGZYDG)对小鼠化学性肝损伤的保护作用及其机制。方法:分别采用四氯化碳(CCl_4)皮下注射小鼠和D-半乳糖胺盐酸盐(D-GalN)腹腔注射小鼠,建立化学性肝损伤模型。各型肝损伤实验中,均把昆明种小鼠随机分为正常对照组(NC),肝损伤模型组,YGZYDG高(YGZYDG_H)、YGZYDG中(YGZYDG_M)、YGZYDG低(YGZYDG_L)剂量组,阳性对照组。观察小鼠肝脏重量指数,脾脏重量指数,胸腺重量指数;测定血清ALT、AST、碱性磷酸酶(AKP)活性,总抗氧化能力(T-AOC)以及血清白蛋白(Alb)含量;肝组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性。HE染色观察各组小鼠肝细胞损伤程度。结果:与模型组比较,YGZYDG对脾脏重量无明显影响,能减轻肝脏和胸腺重量;降低血清ALT、AST、AKP活性,肝组织MDA含量;提高T-AOC水平,增加血清Alb含量、肝组织SOD活性(P<0.01或P<0.05);能够减轻肝细胞损伤程度。结论:YGZYDG对小鼠化学性肝损伤具有保护作用,其机制可能与其抗氧自由基、抑制脂质过氧化作用有关。
目的:研究乙肝转阴颗粒(YGZYDG)对四氯化碳(Carbon tetra-Chloride, CCl_4)所致大鼠肝纤维化的治疗作用,并探讨其作用机制。
方法:Wistar大鼠随机分成两组,模型组大鼠采用50% CCl_4花生油溶液i.g.造模,共8周,正常组用NS代替。将病理检查确认肝纤维化形成的Wistar大鼠50只,随机分成5组,分别给予相应药物进行干预,每日1次,连续5周。末次给药24 h后处死大鼠。
(1)采集血清及肝组织,检测大鼠血清中ALT、AST和肝组织中Hyp、SOD、MDA、GSH-PX的含量。观察肝脏重量指数,脾脏重量指数,胸腺重量指数;
(2)于肝左叶同一部位取肝组织约1 cm×1 cm×l cm大小,固定于4%多聚甲醛溶液,HE染色观察各组大鼠肝脏纤维程度。(3)以RT-PCR法检测肝组织中Col-I、TIMP-1、TGF-β1 mRNA的表达。
结果:
(1)与模型组比较,YGZYDG不同程度的降低肝指数和胸腺指数(P<0.01或P<0.05);但对脾脏重量无明显影响。
(2)与模型组比较,各剂量的乙肝转阴颗粒及阳性药能显著降低大鼠血清中CCl_4所致异常升高的ALT和AST(P<0.01);同时,各剂量的乙肝转阴颗粒能显著提高肝组织中异常降低的SOD、GSH-PX含量(P<0.05或P<0.01),并显著降低异常升高的Hyp、MDA含量(P<0.05或P<0.01)。
(3)HE染色病理结果显示,与模型组比较,乙肝转阴颗粒高、中、低剂量及阳性组大鼠肝脏纤维化程度明显减轻(P<0.05或P<0.01)。
(4)YGZYDG各剂量组和阳性药均可不同程度地下调TIMP-1、TGF-β1 mRNA的表达(P<0.01);YGZYDG高、中剂量组和阳性药可显著下调Col-I mRNA的表达(P<0.01)。
结论:乙肝转阴颗粒对大鼠化学性肝损伤具有一定程度的治疗作用,其机制可能是清除自由基,抑制脂质过氧化,同时抑制胶原合成与沉积,减少细胞外基质(ECM)的沉积和促进ECM的降解。
目的:研究乙肝转阴颗粒及其含药血清对HSC-T6增殖以及相关基因的的影响,探讨其抗肝纤维化的作用机制。方法体外培养大鼠肝星状细胞(HSC-T6),MTT法检测乙肝转阴颗粒及其含药血清对HSC-T6的抑制作用。RT-PCR法测定其对Col-I、TIMP-1及TGF-β1mRNA表达的影响。结果:乙肝转阴颗粒及其含药血清可显著抑制HSC-T6的增殖;YGZYDG各浓度组可显著下调细胞Col-I、TIMP-1、TGF-β1mRNA的表达(P<0.01);YGZYDGS各浓度组可显著下调细胞TIMP-1、TGF-β1mRNA的表达(P<0.01);YGZYDGS高、中浓度组可下调细胞Col-I mRNA的表达(P<0.05或P<0.01)。结论乙肝转阴颗粒及其含药血清可抑制肝星状细胞增殖,并抑制胶原蛋白的生成、促进ECM的降解,这可能是其抗肝纤维化的作用机制之一。
Objective: To observe the protective effect of Yiganzhuanyin Granules (YGZYDG) on acute chemical liver injury in mice. Methods: Two methods of setting chemical-induced liver injury mice models by separately using subcutaneous injection of CCl_4 and intraperitoneal injection of D-GalN Kunming mice were randomly divided into NC group, liver-injured group, high-, medium- and low-dose of YGZYDG groups (0.4, 0.2 and 0.1 g?kg-1 respectively), and biphenyldicarboxylate (BPDC) group. The indexes of liver, spleen and thymus were observed. The activities of ALT, AST and AKP, the ability of T-AOC in serum, the content of Alb; the content of MDA, and the activity of SOD in liver tissue were investigated. Hematoxylineosin (HE) stain was used to examine the degree of hepatic injury. Results: Compared with model group, YGZYDG had no effect on the weight of spleen, but could obviously reduce the weights of liver and thymus; The activities of ALT, AST and AKP, and the content of MDA could be decreased; the ability of T-AOC, the content of Alb, and the activity of SOD could be increased (P<0.01 or P<0.05). The degree of hepatic injury could be lessened. Conclusion: YGZYDG has protective effect on acute chemical liver injury. The mechanism may be related to attenuating free radical and inhibiting the effect on lipid peroxidation.
Objective: To study the effect of YGZYDG against CCl_4-induced liver fibrosis in rats and its mechanism.
Methods: Wistar rats were divided into two groups randomly: hepatic fibrosis model group and normal control group.The rats of Hepatic fibrosis model group were established by intragastric administration (i.g.) of 50% CCl_4 for 8 weeks, and the rats in the normal control group, normal saline (NS) were given too. 50 Wistar rats of hepatic fibrosis group that confirmed by the pathological inspection were divided into 5 groups randomly. All rats were treated with drugs or NS for five consecutive weeks by i.g., one time a day. 24 hours after the last administration of drugs, all rats were killed.
(1) The blood serum and hepatic tissue were taken, and the activities of ALT, AST in serum and the contents of Hyp, SOD, MDA, GSH-PX in hepatic tissue were measured. The indexes of liver, spleen and thymus were observed.
(2) Pieces of hepatic tissues in the identical spot of liver, size 1 cm×1 cm×l cm, were taken, were soaked in 4% paraformaldehyde solution. Hematoxylineosin (HE) stain was used to examine the degree of hepatic fibrosis in rats.
(3) The expressions of Col-I, TIMP-1and TGF-β1 mRNA in hepatic tissue were determined by RT-PCR.
Results:
(1) Compared with model group, YGZYDG could obviously reduce the weights of liver and thymus, but had no effect on the weight of spleen.
(2) Compared with the model control group, the activity of ALT and AST in serum was decreased significantly in all YGZYDG groups and positive control group (P <0.01); the contents of SOD、GSH-PX in hepatic tissue were increased significantly in all YGZYDG groups and positive control group (P<0.05 or P<0.01); and the contents of Hyp、MDA were decreased significantly in the meantime (P<0.05 or P<0.01).
(3) The pathological results of HE staining showed that, compared with the model control group, the rank of hepatic fibrosis in rats of YGZYDGH, YGZYDGM,YGZYDGL and colchicines was significantly lower (P<0.05 or P<0.01).
(4) The expressions of TIMP-1 and TGF-β1 mRNA were down-regulated by all dose of YGZYDG(P<0.01); Col-I mRNA were down-regulated by YGZYDGH, YGZYDGM and colchicine (P<0.01).
Conclusion: YGZYDG might have certain curative effect on CCl_4-induced liver fibrosis in rats,its mechanism may be related to attenuating free radical, inhibiting the lipid peroxidation, reducing the collagen synthesis and the deposition, decreasing the sedimentation of ECM and increasing the degradation of ECM.
Objective:To investigate the effects and mechanism of YGZYDG and its drug serum on the proliferation, related gene of HSC-T6. Method:HSC-T6 was cultured in vitro, and MTT assay was used to evaluate the inhibitive effect of YGZYDG. and the expressions of Col-I, TIMP-1 and TGF-β1 mRNA were determined by RT-PCR. Result : YGZYDG could obviously inhibit the proliferation of HSC-T6; the expressions of Col-I, TIMP-1 and TGF-β1 mRNA were down-regulated by each concentration of YGZYDG (P<0.01); TIMP-1, TGF-β1 mRNA were down-regulated by each concentration of YGZYDGS (P<0.01); Col-I mRNA was up-regulated by YGZYDGSH, YGZYDGSM (P<0.05 or P<0.01). Conclusion:YGZYDG could inhibit the proliferation of HSC-T6, reduce the collagen synthesis, decrease the sedimentation of ECM and increase the degradation of ECM, it might be one of its mechanism of anti-hepatic fibrosis.
目的:研究乙肝转阴颗粒(YGZYDG)对四氯化碳(Carbon tetra-Chloride, CCl_4)所致大鼠肝纤维化的治疗作用,并探讨其作用机制。
方法:Wistar大鼠随机分成两组,模型组大鼠采用50% CCl_4花生油溶液i.g.造模,共8周,正常组用NS代替。将病理检查确认肝纤维化形成的Wistar大鼠50只,随机分成5组,分别给予相应药物进行干预,每日1次,连续5周。末次给药24 h后处死大鼠。
(1)采集血清及肝组织,检测大鼠血清中ALT、AST和肝组织中Hyp、SOD、MDA、GSH-PX的含量。观察肝脏重量指数,脾脏重量指数,胸腺重量指数;
(2)于肝左叶同一部位取肝组织约1 cm×1 cm×l cm大小,固定于4%多聚甲醛溶液,HE染色观察各组大鼠肝脏纤维程度。(3)以RT-PCR法检测肝组织中Col-I、TIMP-1、TGF-β1 mRNA的表达。
结果:
(1)与模型组比较,YGZYDG不同程度的降低肝指数和胸腺指数(P<0.01或P<0.05);但对脾脏重量无明显影响。
(2)与模型组比较,各剂量的乙肝转阴颗粒及阳性药能显著降低大鼠血清中CCl_4所致异常升高的ALT和AST(P<0.01);同时,各剂量的乙肝转阴颗粒能显著提高肝组织中异常降低的SOD、GSH-PX含量(P<0.05或P<0.01),并显著降低异常升高的Hyp、MDA含量(P<0.05或P<0.01)。
(3)HE染色病理结果显示,与模型组比较,乙肝转阴颗粒高、中、低剂量及阳性组大鼠肝脏纤维化程度明显减轻(P<0.05或P<0.01)。
(4)YGZYDG各剂量组和阳性药均可不同程度地下调TIMP-1、TGF-β1 mRNA的表达(P<0.01);YGZYDG高、中剂量组和阳性药可显著下调Col-I mRNA的表达(P<0.01)。
结论:乙肝转阴颗粒对大鼠化学性肝损伤具有一定程度的治疗作用,其机制可能是清除自由基,抑制脂质过氧化,同时抑制胶原合成与沉积,减少细胞外基质(ECM)的沉积和促进ECM的降解。
目的:研究乙肝转阴颗粒及其含药血清对HSC-T6增殖以及相关基因的的影响,探讨其抗肝纤维化的作用机制。方法体外培养大鼠肝星状细胞(HSC-T6),MTT法检测乙肝转阴颗粒及其含药血清对HSC-T6的抑制作用。RT-PCR法测定其对Col-I、TIMP-1及TGF-β1mRNA表达的影响。结果:乙肝转阴颗粒及其含药血清可显著抑制HSC-T6的增殖;YGZYDG各浓度组可显著下调细胞Col-I、TIMP-1、TGF-β1mRNA的表达(P<0.01);YGZYDGS各浓度组可显著下调细胞TIMP-1、TGF-β1mRNA的表达(P<0.01);YGZYDGS高、中浓度组可下调细胞Col-I mRNA的表达(P<0.05或P<0.01)。结论乙肝转阴颗粒及其含药血清可抑制肝星状细胞增殖,并抑制胶原蛋白的生成、促进ECM的降解,这可能是其抗肝纤维化的作用机制之一。
Objective: To observe the protective effect of Yiganzhuanyin Granules (YGZYDG) on acute chemical liver injury in mice. Methods: Two methods of setting chemical-induced liver injury mice models by separately using subcutaneous injection of CCl_4 and intraperitoneal injection of D-GalN Kunming mice were randomly divided into NC group, liver-injured group, high-, medium- and low-dose of YGZYDG groups (0.4, 0.2 and 0.1 g?kg-1 respectively), and biphenyldicarboxylate (BPDC) group. The indexes of liver, spleen and thymus were observed. The activities of ALT, AST and AKP, the ability of T-AOC in serum, the content of Alb; the content of MDA, and the activity of SOD in liver tissue were investigated. Hematoxylineosin (HE) stain was used to examine the degree of hepatic injury. Results: Compared with model group, YGZYDG had no effect on the weight of spleen, but could obviously reduce the weights of liver and thymus; The activities of ALT, AST and AKP, and the content of MDA could be decreased; the ability of T-AOC, the content of Alb, and the activity of SOD could be increased (P<0.01 or P<0.05). The degree of hepatic injury could be lessened. Conclusion: YGZYDG has protective effect on acute chemical liver injury. The mechanism may be related to attenuating free radical and inhibiting the effect on lipid peroxidation.
Objective: To study the effect of YGZYDG against CCl_4-induced liver fibrosis in rats and its mechanism.
Methods: Wistar rats were divided into two groups randomly: hepatic fibrosis model group and normal control group.The rats of Hepatic fibrosis model group were established by intragastric administration (i.g.) of 50% CCl_4 for 8 weeks, and the rats in the normal control group, normal saline (NS) were given too. 50 Wistar rats of hepatic fibrosis group that confirmed by the pathological inspection were divided into 5 groups randomly. All rats were treated with drugs or NS for five consecutive weeks by i.g., one time a day. 24 hours after the last administration of drugs, all rats were killed.
(1) The blood serum and hepatic tissue were taken, and the activities of ALT, AST in serum and the contents of Hyp, SOD, MDA, GSH-PX in hepatic tissue were measured. The indexes of liver, spleen and thymus were observed.
(2) Pieces of hepatic tissues in the identical spot of liver, size 1 cm×1 cm×l cm, were taken, were soaked in 4% paraformaldehyde solution. Hematoxylineosin (HE) stain was used to examine the degree of hepatic fibrosis in rats.
(3) The expressions of Col-I, TIMP-1and TGF-β1 mRNA in hepatic tissue were determined by RT-PCR.
Results:
(1) Compared with model group, YGZYDG could obviously reduce the weights of liver and thymus, but had no effect on the weight of spleen.
(2) Compared with the model control group, the activity of ALT and AST in serum was decreased significantly in all YGZYDG groups and positive control group (P <0.01); the contents of SOD、GSH-PX in hepatic tissue were increased significantly in all YGZYDG groups and positive control group (P<0.05 or P<0.01); and the contents of Hyp、MDA were decreased significantly in the meantime (P<0.05 or P<0.01).
(3) The pathological results of HE staining showed that, compared with the model control group, the rank of hepatic fibrosis in rats of YGZYDGH, YGZYDGM,YGZYDGL and colchicines was significantly lower (P<0.05 or P<0.01).
(4) The expressions of TIMP-1 and TGF-β1 mRNA were down-regulated by all dose of YGZYDG(P<0.01); Col-I mRNA were down-regulated by YGZYDGH, YGZYDGM and colchicine (P<0.01).
Conclusion: YGZYDG might have certain curative effect on CCl_4-induced liver fibrosis in rats,its mechanism may be related to attenuating free radical, inhibiting the lipid peroxidation, reducing the collagen synthesis and the deposition, decreasing the sedimentation of ECM and increasing the degradation of ECM.
Objective:To investigate the effects and mechanism of YGZYDG and its drug serum on the proliferation, related gene of HSC-T6. Method:HSC-T6 was cultured in vitro, and MTT assay was used to evaluate the inhibitive effect of YGZYDG. and the expressions of Col-I, TIMP-1 and TGF-β1 mRNA were determined by RT-PCR. Result : YGZYDG could obviously inhibit the proliferation of HSC-T6; the expressions of Col-I, TIMP-1 and TGF-β1 mRNA were down-regulated by each concentration of YGZYDG (P<0.01); TIMP-1, TGF-β1 mRNA were down-regulated by each concentration of YGZYDGS (P<0.01); Col-I mRNA was up-regulated by YGZYDGSH, YGZYDGSM (P<0.05 or P<0.01). Conclusion:YGZYDG could inhibit the proliferation of HSC-T6, reduce the collagen synthesis, decrease the sedimentation of ECM and increase the degradation of ECM, it might be one of its mechanism of anti-hepatic fibrosis.
引文
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