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纸质出版日期:2017
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谢君, 谢晓芳, 代良萍, 等. 肝苏颗粒对四氯化碳致肝纤维化大鼠肝功能和病理损伤的影响[J]. 中国实验方剂学杂志, 2017,23(8):117-123.
XIE Jun, XIE Xiao-fang, DAI Liang-ping, et al. Effect of Gansu Granule on Liver Function and Liver Damage for Perchlormethane-induced Hepatic Fibrosis of Rats[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(8): 117-123.
谢君, 谢晓芳, 代良萍, 等. 肝苏颗粒对四氯化碳致肝纤维化大鼠肝功能和病理损伤的影响[J]. 中国实验方剂学杂志, 2017,23(8):117-123. DOI: 10.13422/j.cnki.syfjx.2017080117.
XIE Jun, XIE Xiao-fang, DAI Liang-ping, et al. Effect of Gansu Granule on Liver Function and Liver Damage for Perchlormethane-induced Hepatic Fibrosis of Rats[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(8): 117-123. DOI: 10.13422/j.cnki.syfjx.2017080117.
目的:探讨肝苏颗粒对四氯化碳(CCl4)诱导的大鼠肝纤维化的防治作用及作用机制。方法:将72只大鼠随机分为正常组、模型组、秋水仙碱组(0.1 mg·kg-1)和肝苏颗粒高、中、低剂量组(16.7,8.4,4.2 g·kg-1),每组12只,CCl4建立大鼠肝纤维化模型,同时灌胃给药10周。末次给药后,取血检测大鼠肝功能和重要脏器指数,酶联免疫吸附测定法(ELISA)测定肝组织中透明质酸(HA),层连蛋白(LN),基质金属蛋白酶1(MMP-1)和金属蛋白酶抑制因子1(TIMP-1)含量;另取肝组织行一般病理学检查和马松(Masson)染色纤维化观察,并免疫组化法测定肝组织中α-平滑肌肌动蛋白(α-SMA),转化生长因子-β1(TGF-β1)的表达。结果:与正常组比较,模型组大鼠血清丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST),总胆红素(TBIL),血清碱性磷酸酶(ALP)明显升高,总蛋白(TP)明显下降(P<0.01),肝组织HA,LN,TIMP-1水平明显升高(P<0.01),肝,脾系数显著升高而胸腺系数降低(P<0.01),肝脏质地变硬,病理学检测见典型假小叶形成,免疫组化检测显示肝组织TGF-β1,α-SMA表达明显增强。秋水仙碱组和肝苏颗粒各组大鼠血清ALT,AST,ALP,TBIL水平均显著下降,球蛋白明显增加(P<0.01),肝苏颗粒低剂量组的白蛋白(ALB)含量明显增加(P<0.05);各给药组肝组织中HA,TIMP-1水平明显降低(P<0.01),纤维化程度有不同程度改善,肝组织TGF-β1,α-SMA表达减弱。结论:肝苏颗粒对CCl4致大鼠肝纤维化有显著治疗作用,能明显改善肝功能,减轻肝脏纤维化病变,机制与减轻肝细胞损伤和抑制纤维病变发展有关。
Objective: To observe the preventive effect and action mechanism of Gansu granule on hepatic fibrosis rats induced by perchlormethane (CCl4). Method: The liver fibrosis model of rats was established by CCl4.Totally 72 male rats were randomly divided into 6 groups
namely normal control group(n=12)
model control group (n=12)
colchicine group (n=12
0.1 mg·kg-1)
and high
medium and low-dose Gansu granule groups (n=12
16.7
8.4
4.2 g·kg-1). Ten weeks later after drug administration
all of the rats were put to death. Blood was collected to detect liver indexes
such as alanine transaminase(AST)
aspartate aminotransferase(ALT)
total bilirubin(TBIL)
total protein(TP)
ALB
and alkaline phosphatase (ALP). Besides
the liver
spleen and thymus gland were dissected and weighed. Liver hyaluronic acid (HA)
layer even protein (LN)
Matrix metalloproteinases-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were determined by enzyme-linked immunoassay assay (ELISA). Pathological histology observation by HE staining and Masson staining were performed for other liver tissues. Alpha-smooth muscle actin (α-SMA) and transforming growth factor β(TGF-β) expression in the hepatic tissue were measured by immunohistochemical method. Result: Compared with normal control group
model control group's rats serum ALT
AST
TBIL and ALP contents were significantly increased
PT significantly decreased (P<0.01)
liver tissue HA
LN
TIMP-1 levels were increased significantly (P<0.01)
with remarkable increase in liver
spleen coefficients (P<0.01) and decrease of thymus gland coefficient. The liver texture of model rats was harden
with formation of pseudolobule and increase in expressions of TGF-β
and α-SMA in the liver. Compared with model control group
serum ALT
AST
ALP
TBIL levels were significantly declined and globulin increased significantly in both colchicine group and Gansu granule groups (P<0.01)
and albumin level in low-dose Gansu granule group was obviously increased (P<0.05). For all of drug treating groups
the contents of HA and TIMP-1 in liver tissues were significantly decreased (P<0.01)
the degree of fibrosis were alleviated
and TGF-β1
α-SMA expressions in liver reduced. Conclusion: Gansu granule has an obvious anti-hepatic fibrosis effect
and can significantly improve the liver function and reduce the liver fibrosis for model rats. The action mechanism is correlated with reduction of liver cell damage and prevention of fibrosis.
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