基于“有故无殒”的何首乌对正常和肝损伤大鼠的毒性与保护作用对比研究  

The toxic and protective effects of Polygonum multiflorum on normal and liver injured rats based on the symptom-based prescription theory

作　　者：庞晶瑶 柏兆方[1] 牛明[1] 涂灿[1] 马致洁[2] 赵艳玲[1] 赵奎君[2] 游云[3] 王伽伯[1] 肖小河[4] 

机构地区：[1]解放军302医院全军中医药研究所,北京100039 [2]首都医科大学附属北京友谊医院,北京100050 [3]中国中医科学院中药研究所,北京100700 [4]解放军302医院中西医结合肝病诊疗与研究中心,北京100039

出　　处：《药学学报》2015年第8期973-979,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81373984);国家"重大新药创制"科技重大专项资助项目(2015ZX09501-004-001-008);国家公益性行业科研专项资助项目(201507004-04);中国中医科学院客座研究员联合创新研究项目(ZZ070827)

摘　　要：本研究采用正常和CCl4致慢性肝损伤模型大鼠,何首乌给药剂量分别为生药10和20 g·kg-1,考察何首乌50%醇提物对大鼠的一般状态、生化指标、细胞因子及组织病理的影响,并通过因子分析方法综合评价不同剂量何首乌在不同大鼠模型上的量-效/毒应答差异。结果显示,与正常对照组相比,正常高剂量组丙氨酸转氨酶(ALT)、总胆红素(TBIL)、高迁移率族蛋白1(HMGB-1)和白细胞介素-1β(IL-1β)显著升高(P<0.05或P<0.01),肝脏病理切片可见炎细胞浸润、肝窦扩大及纤维条索形成;与模型对照组相比,模型低剂量组ALT、天冬氨酸转氨酶(AST)和总胆汁酸(TBA)显著下降(P<0.05),肝脏病理切片显示肝细胞空泡变性有所减轻,但仍可见大量炎细胞浸润和纤维组织增生,而模型高剂量组HMGB-1、肿瘤坏死因子-α(TNF-α)和IL-1β显著下降(P<0.05或P<0.01),肝细胞空泡变性、炎细胞浸润及纤维化程度都明显减轻。因子分析结果表明,低剂量何首乌对正常大鼠的损伤作用以及对模型大鼠的保护作用均不明显;高剂量的何首乌对正常大鼠的损伤作用表现在公因子-1(HMGB-1、TNF-α和IL-1β为主要贡献)和公因子-2(TBIL、ALT和TBA为主要贡献)均显著升高,与正常对照组差异显著;高剂量对模型大鼠的保护作用主要表现在公因子-1显著下降,提示高剂量何首乌可显著降低炎症因子的表达。结果表明,何首乌对肝脏的作用具有"有故无殒"现象,表现为高剂量何首乌可导致正常动物肝损伤,但对于慢性肝损伤模型动物具有肝保护和治疗作用。The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CC14-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase （ALT）, total bilirubin （TBIL）, high mobility group box 1 （HMGB-1） and interleukin-1β （IL-1β） （P〈0.05 or P〈0.01）, as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase （AST） and total bile acid （TBA） （P〈0.05）, as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α （TNF-α） and IL-1β （P〈0.05, P〈0.01）, as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 （HMGB-1, TNF-α and IL-1β as the main contributors） and factor-2 （TBIL, ALT and TBA as the main contributors） relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor- 1, indicating the effective alleviation of the expression of

关 键 词：何首乌 肝损伤 有故无殒 双向作用 炎症因子 

分 类 号：R285[医药卫生—中药学]