Effect of Ganduqing Granule on metabolic disorder and liver dysfunction in patients with chronic hepatitis B

目的:探讨肝毒清胶囊改善慢性乙型肝炎患者肝功能异常的潜在机制.方法:采集30例乙型肝炎患者经肝毒清胶囊治疗前、后的血浆以及30例正常健康人的血浆,分别检测其肝功能,并使用超高效液相色谱-质谱联用法检测胆汁酸、脂质和肝脏氧化应激代谢产物的变化.结果:与正常对照组比较,慢性乙肝患者的肝功能明显异常,血浆中有8种代谢产物(3-硫酸甘氨鹅脱氧胆酸、甘氨鹅脱氧胆酸-3-葡萄糖醛酸,牛磺鹅脱氧胆酸,胆烷酸,二羟基雄甾烯酮硫酸,溶血磷脂酰胆碱(C18:3),溶血磷脂酰乙醇胺(C22:1);2,6-二氨基-4-羟基-5-N-甲基甲酰嘧啶)明显升高(P<0.05).经肝毒清胶囊治疗3周后,这8种升高的代谢产物均显著降低(P<0.05),并趋于正常水平.其中,3-硫酸甘氨鹅脱氧胆酸、甘氨鹅脱氧胆酸-3-葡萄糖醛酸,牛磺鹅脱氧胆酸和胆烷酸与胆汁酸代谢有关;二羟基雄甾烯酮硫酸,溶血磷脂酰胆碱(C18:3)和溶血磷脂酰乙醇胺(C22:1)与脂质代谢有关;2,6-二氨基-4-羟基-5-N-甲基甲酰嘧啶与肝脏的氧化应激相关.同时,血清中丙氨酸转氨酶,天冬氨酸转氨酶,总胆红素;直接胆红素和HBV病毒水平明显降低(均P<0.05).结论:肝毒清胶囊通过改善慢性乙肝患者的脂质代谢、胆汁酸代谢及氧化应激反应等,进而改善其肝功能.

Objective:This study investigated the potential mechanisms of Ganduqing Granule(GDQG)in improving the liver function in patients with chronic hepatitis B(CHB).Methods:Plasma samples from 30 healthy volunteers and 30 patients with CHB before and after the treatment with GDQG were measured for the alterations in liver function and metabolites,using the method of ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry.Results:Patients with CHB developed severe liver dysfunction,which was associated with the higher plasma levels of 8 metabolites when compared with those of the normal control(P<0.05).Interestingly,after treatment with GDQG for 3 weeks,the 8 metabolites were significantly reduced(P<0.05).Among them,glycochenodeoxycholate-3-sulfate,glycochenodeoxycholic acid-3-glucuronide,taurochenodeoxycholic acid,and 7b-hydroxy-3-oxo-5b-cholanoic acid were associated with the metabolism of bile acids,while 3b,16a-dihydroxyandrostenone sulfate,lysophosphatidylcholine(C18:3),and lysophosphatidylethanolamine(C22:1)were related to the metabolism of lipids.2,6-Diamino-4-hydroxy-5-N-methylformamidopyrimidine was related to hepatic oxidative stress.Meanwhile,liver damage in patients was greatly reduced.Conclusion:Treatment with GDQG has improved liver function of patients with CHB through the possible mechanism of adjusting the metabolic disorders related to lipids,bile acids,and oxidative stress.