牛磺酸降低高胆固醇HepG2细胞内胆固醇的作用机制研究

目的:探讨牛磺酸对高胆固醇Hep G2细胞胆固醇降解作用及其机制。方法:以0.02 mmol/L胆固醇加入培养液中建立高胆固醇细胞模型后,分别加入1、10、20 mmol/L牛磺酸培养48 h,测定细胞内总胆固醇（TC）、游离胆固醇（FC）、胆固醇酯（EC）及细胞内总胆汁酸（TBAc）和培养液总胆汁酸（TBAm）水平;并检测20 mmol/L牛磺酸作用24 h后细胞CYP7A1及其调控分子的蛋白表达水平。结果:10 mmol/L和20 mmol/L牛磺酸作用48 h可显著降低细胞内TC、FC和EC（p<0.01）,同时升高了TBAc和TBAm（p<0.05或p<0.01）;20 mmol/L牛磺酸作用24 h时使CYP7A1显著增加（p<0.05）;20 mmol/L牛磺酸作用24 h后MAPK、ERK、JNK、c-jun和p-c-jun表达明显降低（p<0.05）,而对HNF4α则无显著影响。结论:牛磺酸可抑制高胆固醇Hep G2细胞MAPK/ERK和MAPK/JNK表达水平,降低c-jun蛋白表达及c-jun磷酸化水平,促进CYP7A1蛋白表达升高,从而加速胆固醇转化为胆汁酸。 

Cholesterol- lowering effect of taurine and its mechanism in high- cholesterol Hep G2 cells

Objective: To study the effect of taurine on cholesterol degradation and its preliminary mechanism.Methods: Hep G2 cells were treated with 1,10,and 20 mmol / L taurine for 48 h after being cultured in DMEM supplemented with 0.02 mmol / L cholesterol. Then the levels of intracellular total cholesterol( TC),free cholesterol( FC),ester cholesterol( EC),total bile acids( TBAc) and medium TBA( TBAm) were determined.The expression of CYP7A1 and its regulatory key molecules were detected by western blot after Hep G2 cells were incubated with20 mmol / L taurine for 24 h.Results: TC,FC and EC were significantly reduced and TBAc and TBAm were increased by 10 mmol / L and 20 mmol / L taurine for 48 h- treatment( p < 0.05 or p < 0.01). The expression of CYP7A1 was significantly increased by 20 mmol / L taurine at 24 h( p < 0.05).The expression of MAPK,ERK,JNK,c- jun and p- c- jun were obviously decreased( p < 0.05) and the expression of HNF4α had no significant change by 20 mmol / L taurine for 24 h. Conclusion: Taurine can enhance CYP7A1 expression by inhibiting MAPK / JNK,MAPK / ERK and c- Jun / p- c- Jun expression,to promote the transformation of cholesterol to bile acid in liver cells.