大黄总蒽醌对免疫性肝纤维化大鼠的保护作用及机制探讨  

Protective effect and mechanism of rhubarb total anthraquinones on immune hepatic fibrosis in rats

作　　者：宋献美 王雪银 李宁宁 崔伟锋[2] 梁瑞峰[2] SONG Xian - mei;WANG Xue - yin;LI Ning - ning;CUI Wei - feng;LIANG Rui - Feng(Department of Microbiology and Immunology,Henan Medical College,Zhengzhou,Henan 451191,China)

机构地区：[1]河南医学高等专科学校微生物与免疫学教研室,河南郑州451191 [2]河南省中医药研究院中药研究所,河南郑州450004

出　　处：《现代预防医学》2018年第15期2818-2822,共5页Modern Preventive Medicine

基　　金：河南省科技攻关计划(No.162102310373);河南省中医药科学研究专项(No.2015ZY2072)

摘　　要：目的探索大黄总蒽醌对免疫性肝纤维化大鼠的作用及对基质金属蛋白酶-13(MMP-13)和基质金属蛋白酶抑制剂-1(TIMP-1)的调控。方法 SD大鼠按体重随机分为正常组、模型组、秋水仙碱阳性组、大黄总蒽醌低、中、高剂量组,除正常组外,其余大鼠均腹腔注射猪血清建立免疫性肝纤维化模型。从第7周开始灌胃给药,每天1次,连续60d,末次给药后,分析血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)的活性和层粘连蛋白(LN)、透明质酸(HA)、Ⅳ型胶原(PCⅢ)的含量,观察肝组织病理学改变,Western blot分析MMP-13和TIMP-1的蛋白表达。结果与正常组比较,模型组大鼠ALT、AST、LN、HA和Ⅳ-C水平显著升高,肝组织中MMP-13水平降低,TIMP表达增加(P<0.05);与模型组相比,大黄总蒽醌中、高剂量组大鼠ALT、AST、LN、HA和Ⅳ-C的水平均不同程度地降低,肝中MMP-13的表达增加,TIMP的表达减少(P<0.05);病理显示,各给药组均能减轻猪血清造成的肝损伤。结论大黄总蒽醌可有效改善肝纤维化,其机制可能与MMP-13、TIMP-1的表达调控有关。Objective To research the rhubarb total anthraquinones on immune hepatic fibrosis in rats and modulatory effect on MMP - 13 and TIMP - 1 expression. Methods SD rats were randomly divided into normal group, model group, colchicine group ,low, medium and high dose group of rhubarb total anthraquinones. The models were established by intraperitoneal injection of porcine serum. From week 7 after modeling, appropriate drugs were administrated via garage once a day for 60 days. The activities of serum alanin aminotransferase （ ALT）, aspartate aminotransferase （AST） and the contents of laminin （LN） , hyaluronic acid （ HA ） and Collagen Ⅳ （ Ⅳ - C ） in serum were detected after the last drug. Liver pathology was observed. The expression of matrix metalloproteinase - 13 （ MMP - 13 ） and tissue inhibitor of metalloproteinase - 1 （ TIMP - 1 ） in liver were analyzed by Western blot. Results Compared with the normal group, the levels of ALT, AST, LN, HA and Ⅳ - C of model rats were significantly increased. The expression of MMP - 13 in liver was reduced while the expression of TIMP - 1 was increased （ P 〈 0. 05 ）. Compared with the model group, the levels of ALT, AST, ALP, LN, HA, IV - C and the expression of TIMP- 1 decreased in medium and high dose group of rhubarb total anthraquinones, while the expression of MMP- 13 significantly increased （ P 〈 0. 05 ）. The liver pathological fibrosis was obviously relieved in experimental groups. Conclusion Rhubarb total anthraquinones have protective effect on the rats with immune - mediated hepatic fibrosis. The effect is associated with upregnlation of MMP - 13 and downregnlation of TIMP - 1.

关 键 词：免疫性肝纤维化 大黄总蒽醌 猪血清 MMP-13 T1MP-1 

分 类 号：R113[医药卫生—公共卫生与预防医学]