布拉氏酵母菌散剂对NASH大鼠的疗效及其作用机制探讨

目的观察口服布拉氏酵母菌散剂对NASH大鼠的疗效及其对sR—A的影响。方法42只雄性Sprague Dawley（SD）大鼠，随机分为正常对照组（NG，n=14）、模型组（MG，n=14）和干预组（TB，n=14）；正常组给予普通饲料喂养，模型组给予高脂饲料喂养，17周起干预组给予布拉氏酵母菌散剂灌胃，24周末将所有大鼠一并处死。比较各组血清内毒素、谷丙转氨酶、谷草转氨酶；计算非酒精性脂肪性肝病评分；采用免疫荧光法测定SR—A蛋白的表达，RealtimePCR法检测大鼠肝脏SR-A、TNF—αmRNA水平。结果与正常对照组相比，模型组的大鼠门冬氨酸氨基转氨酶（AST）、丙氨酸氨基转氨酶（ALT）均明显升高；干预组的大鼠AST、ALT与模型组相比均下降；模型组血清内毒素水平与正常对照组相比明显增加（0．36±0．02）EU／mL vs（0．17±0．01）EU／mL，P〈0．05]；而与模型组相比，干预组血清内毒素水平减少（0．22±0．01）EU／mL vs（0．36±0．02）EU／Ml，P〈0．05）。肝组织SR—A在正常对照组呈弥漫性表达，模型组肝脏的表达明显减少，干预组肝组织SR—A的表达较模型组升高。模型组的大鼠肝组织SR—AmRNA水平与正常组相比显著减少（0．52±0．32vs1．43±0．46，P〈0．05）；而与模型组相比，干预组的大鼠肝组织SR—AmRNA增加（0．87±0．34vs0．52±0．32。P〈0．05）。与正常组相比，模型组的大鼠肝组织TNF-αmRNA水平明显增加（1．56±0．35vs0．57±0．23，P〈0．05）；而与模型组相比，干预组的大鼠肝组织TNF—dmRNA水平减少（1．23±0．24vs1．564-0．35，P〈0．05）。结论布拉氏酵母菌散剂能够减轻肝脏脂肪变性及炎症程度，其机制可能与改善肠道菌群、减少肠源性内毒素、增加肝组织SR-A的表达有关。

Discussion on mechanism and effect of Saccharomyces boulardii in rats with nonalcoholic steatohepatitis

Objective To observe the influence of oral administration of Saceharomyces boulardii on SR-A in rats with nonalcoholic steatohepatitis （NASH） induced by high-fat diet. Methods Forty-two male Sprague-Dawley （SD） rats were divided randomly into normal control group（ NG, n = 14）fed with normal diet, model group（ MG, n = 14）and intervention group（TB,n = 14）both fed with high-fat diet From 17th week,Rats in intervention group were administrated with oral Saecharomyees boulardii. At the end of 24th week, all rats were sacrificed. The endo- toxin level, AST and ALT were detected. NAS score was evaluated. The protein of SR-A were detected by immuno-fluorescence and mRNA levels of hepatic SR-A and TNF-α were detectedby real time PCR. Results Compared with normal group, the levels of AST and ALT in model group increased significantly; the levels of AST and ALT decreased in intervention group compared with those of the model group. The level of serum endotoxin in the model group significantly increased compared with that of the normal control group （ 0.36 ± 0.02） vs （0.17 ± 0.01 ） EU/mL, P 〈 0.05 ）. The level of endotoxin decreased in intervention group compared with that of model group （ 0. 221 ± 0.01 ） EU/mL vs （0.36 ±0.02） EU/mL, P 〈 0.05 ）. The expression of SR-A in normal group was diffused, which decreased significantly in model group. Hepatic SR-A protein expression increased slightly in intervention group. The levels of SR-A mRNA in liver tissues significantly reduced in model group compared with that of normal group （0.52 ±0.32 vs 1.43 ±0.46, P 〈0.05） ; While it increased in intervention group compared with that of model group （0.87 ± 0.34 vs 0. 52 ± 0. 32, P 〈 0.05 ）. Compared with normal group, the levels of TNF-α mRNA in model group increased significantly （ 1.56 ± 0.35 vs 0. 57 ± 0. 23, P 〈 0.05） ; the levels of TNF-α mRNA decreased in intervention group compared with that of the model group （ 1.23± 0. 24 vs 1. 56± 0. 35, P 〈 0.05）. Conclusion Saccharomyces boulardii can reduce the degree of hepatic steatosis and inflammation by means of improving the intestinal flore, reducing intestinal endotoxemia and increasing expression of SR-A in liver tissue.