二黄祛脂方及其精简方对小鼠高血脂的防治作用

Effect of Erhuang Quzhi Decoction and Its Streamlined Formula in Preventing Hyperlipidemia in Mice

目的探讨二黄祛脂方(EHQZF)及其精简方Ⅰ(QZF-Ⅰ)和精简方Ⅱ(QZF-Ⅱ)抗高血脂(HPL)的疗效。方法运用网络药理学中Degree值排序及EHQZF的处方量排序,取前四位中药分别组方为QZF-Ⅰ和QZF-Ⅱ并利用LC-MS检测EHQZF中的主要有效成分;采用抗氧化实验比较EHQZF及精简方的抗氧化效果;取ICR小鼠,随机分为正常组(CON)、高血脂组(HPL)、EHQZF组(2.4 g·kg^(-1))、QZF-Ⅰ组(2.4 g·kg^(-1))、QZF-Ⅱ组(2.4 g·kg^(-1))和阳性药苯扎贝特(BZBT)组(60.67 mg·kg^(-1)),500 mg·kg^(-1) Tyloxapol建立高血脂模型;检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙二醛(MDA)、超氧化物歧化酶(SOD)及肝组织中白细胞介素(IL)-6、IL^(-1)β含量,利用苏木精-伊红(HE)染色和油红O染色进行病理学观察。结果网络药理学结合液相色谱-质谱联用(LC-MS)结果表明,黄酮类和酚酸类是EHQZF抗HPL的主要有效成分;抗氧化实验结果表明,EHQZF、QZF-Ⅰ及QZF-Ⅱ均可抑制ABTS及DPPH自由基;动物实验结果表明,EHQZF、QZF-Ⅰ及QZF-Ⅱ均可显著降低血清ALT、AST、TG、TC、LDL-C水平、抑制MDA水平,升高HDL-C和SOD水平(P<0.05或P<0.01);EHQZF和QZF-Ⅱ均可减少肝组织IL-6和IL^(-1)β含量(P<0.05或P<0.01),其中QZF-Ⅱ效果更好,而QZF-Ⅰ基本不影响IL-6和IL^(-1)β含量,HE染色和油红O染色结果表明,EHQZF、QZF-Ⅰ、QZF-Ⅱ均可改善小鼠血清澄清度和肝脏病理状态、减轻肝脏炎性细胞浸润和脂滴蓄积,其中QZF-Ⅱ效果显著。结论QZF-Ⅱ是抗HPL的最优复方,其可通过抗氧化、改善肝损伤、减轻肝脏炎症和脂滴蓄积防治小鼠HPL。

Objective To investigate the efficacy of EHQZF and its simplified formula:simplified formulaⅠ(QZF-Ⅰ)and simplified formulaⅡ(QZF-Ⅱ)against hyperlipidemia(HPL),which are clinically effective in lowering lipids.Methods Using network pharmacology Degree value ranking and EHQZF's prescription quantity ranking,the top four herbal medicines were taken and grouped into QZF-Ⅰand QZF-Ⅱ,respectively;the antioxidant effects of EHQZF and simplified formula were compared by antioxidant experiment;ICR mice were randomly divided into normal group(CON),hyperlipidemia group(HPL),EHQZF group(2.4 g·kg^(-1)),QZF-Ⅰgroup(2.4 g·kg^(-1)),QZF-Ⅱgroup(2.4 g·kg^(-1))and positive drug benzofibrate(BZBT)group(60.67 mg·kg^(-1)),the establishment of hyperlipidemia model with 500 mg·kg^(-1) tyloxapol;and serum was taken to detect ALT,AST,TG,TC,HDL-C,LDL-C,MDA,SOD,IL-6,and IL^(-1)β;The pathological observation was performed by HE staining and oil red O staining.Results The results of network pharmacology combined with LC-MS showed that flavonoids and phenolic acids were important compounds of EHQZF against HPL;the results of antioxidant experiments showed that EHQZF,QZF-Ⅰand QZF-Ⅱcould inhibit ABTS and DPPH radicals.The results of animal experiments showed that EHQZF,QZF-Ⅰand QZF-Ⅱcould significantly reduce the levels of serum ALT,AST,TG,TC,LDL-C,inhibit the level of MDA,and increase the levels of HDL-C and SOD(P<0.05 or P<0.01);EHQZF and QZF-Ⅱboth reduced IL-6 and IL^(-1)βlevels in liver tissue homogenates(P<0.05 or P<0.01),with QZF-Ⅱhaving a better effect,while QZF-Ⅰbasically did not affect IL-6 and IL^(-1)βlevels.The results of HE staining and Oil Red O staining showed that EHQZF,QZF-Ⅰand QZF-Ⅱcould improve serum clarity and liver pathology,reduce liver inflammatory cell infiltration and lipid droplet accumulation in mice,among which QZF-Ⅱhad the best effect.Conclusion QZF-Ⅱis more effective against HPL in mice through antioxidants,improving liver injury,and reducing liver inflammation and lipid droplet accumulation.