目的观察复方贞术调脂方(FTZ)对高脂饮食致非酒精性脂肪肝的预防作用,并探讨其相关机制。方法 20只雄性C57BL/6j小鼠按随机数表法分为模型组及FTZ组,每组10只。两组均予高脂饮食喂养,同时模型组予5%阿拉伯树胶水溶液灌胃,FTZ组予FTZ浸膏粉溶液灌胃(每日1.17 g/kg,以5%阿拉伯树胶水溶液为溶剂,10 m L/kg灌胃给药),两组每日1次给药,共给药5个月。监测小鼠进食量及体重情况,检测治疗前后小鼠血糖、血脂水平,治疗后进行口服糖耐量实验(OGTT),并计算曲线下面积(AUC)。观察肝脏病理情况,测定肝脏脂质含量,Real-time PCR法检测肝内过氧化物酶体增殖物激活受体α(PPARα)、肉碱脂酰转移酶1(CPT1)m RNA表达。结果两组小鼠进食量相近,差异无统计学意义(P>0.05),但是高脂喂养3个月后FTZ组小鼠体重明显低于模型组(P<0.05)。治疗前,两组TG、TC及空腹血糖比较差异无统计学意义(P>0.05)。治疗后,与模型组比较,FTZ组小鼠TC、TG、空腹血糖、肝脏TC、TG水平降低(P<0.05),OGTT实验AUC明显减少(P<0.05),肝脏中PPARα及CPT1 m RNA表达升高(P<0.05,P<0.01)。两组小鼠肝脏重量、内脏脂肪及腹股沟脂肪称重结果比较,差异无统计学意义(P>0.05)。模型组小鼠可观察到肝脏明显脂质沉积,汇管区周围、中央静脉周围可见大量肝细胞空泡变性及水样变性,淋巴细胞浸润,少量肝细胞点状坏死。而FTZ组肝脏空泡变性及水样变性程度明显轻于模型组。结论 FTZ可延缓高脂饮食所致的非酒精性脂肪肝的发生,其机制与上调肝PPARα及其下游基因CPT1,促进脂肪酸氧化,改善胰岛素敏感性有关。
Hyperlipidemia, type 2 diabetes mellitus, nonalcoholic fatty liver and many other metabolic disorder are frequently co-existing in patients. In addition, these diseases are closely related in pathophysiological settings. However, increasing of the disease incidence, lacking of comprehensive prevention and control measurements against the key pathology point concomitant occurrence with the pattem of the single disease, single target therapy, that is leading therapeutic strategy for these metabolic disorders in the setting of Western medicine （WM）. On the basis of the combination of the advantages of integrated Chinese medicine （CM） and WM, with unified understanding of such diseases, the new concept of glucolipid metabolic disease （GLMD） is introduced. In this new concept, disorders in glucose and lipid metabolism are recognized as the key trigger and major driving force for the progress of GLMD. The key points of pathology included dysfunction of neuronal-endocrine-immune system,insulin resistance, oxidative stress, inflammation and intestinal flora imbalance. In the core pathogenic perspective of CM, it can be explained as ＂Gan （Liver） Shi Shu Xie＂ （dysfunction of Gan in metabolism and emotion regulation） that will lead to the occurence/production of endogenous dampness and phlegm, blood stasis and turbid. This leads to the new concept of ＂Liver-based regulatory system for metabolic homeostasis＂ to be introduced further. The comprehensive prevention and control strategy ＂Tiao Gan Qi Shu Hua Zhuo＂ （modulating Gan, trigging key metabolic system to resolve pathogenic factors such as phlegm retention and dampness）. Its representative formula Fufang Zhenzhu Tiaozhi Capsule （复方贞术调脂胶囊） is innovated under such rationales. Comment for some commonly-used CM GLMD therapeutic drugs was presented. High-level evidence-based and epidemiological and mechanism studies should be carded out to further interpret and explain of the scientific connotation of GLMD.
