大蒜为百合科葱属植物的地下鳞茎,具有药食两用的价值,其含有大蒜素、二烯丙基硫醚、二烯丙基二硫醚、二烯丙基三硫醚、 硫-烯丙基半胱氨酸等多种生物活性成分,具有抗氧化、抗感染、免疫调节、心血管保护、抗癌等作用。不仅如此,大蒜在糖脂代谢的调节中功效显著,且相关机制日益明晰,主要包括保护胰岛β细胞功能、改善胰岛素抵抗、阻止脂肪细胞生长、抑制脂合成代谢及调节肠道菌群分布等。不同的提取工艺可影响大蒜的功效,其提取手段及药效关系值得进一步研究。

Garlic has values of both medicine and food,with rich allicin,diallyl disulfide（DADS）,diallyl trisulfide（DATS）and other garlic sulfur contents,which have been found to have multiple effets such as antioxidant,anti-infection,immunomodulatory,cardiovascular protection,anti-cancer,etc．Moreover,numerous studies have demonstrated that garlic plays an important role in the regulation of glycose and lipid metabolism,and the relevant mechanisms are becoming better understood,including protecting pancreatic β cells,improving insulin resistance,preventing the growth of fat cells,inhibiting lipid anabolism and adjusting the distribution of intestinal microflora．Different extraction processes can affect the efficacy of garlic,and further investigations are needed to elucidate the relationship between effective extraction methods and pharmacodynamic properties．

       目的   探讨NXT629改善肝胆结石形成的相关机制。方法   对C57BL/6J小鼠分别采用常规饮食或成石饮食（LD）喂养，并在LD组小鼠注射PPAR-α拮抗剂NXT629。通过苏木精-伊红染色法染色分析肝脂肪病变，油红O染色检测肝脏脂质的积累，分光光度法检测胆汁或血清中总胆固醇、甘油三酯、磷脂、总胆汁酸、胆固醇饱和指数、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇指标；qPCR法检测小鼠肝组织中ABCG5/8、CYP7A1、CYP7B1、PPAR-α和ABCB11 mRNA的表达情况。结果  NXT629通过靶向PPAR-α降低LD组小鼠肝脏中的ABCG5、ABCG8、ABCB11 mRNA水平以及增加CYP7A1、CYP7B1 mRNA水平，进而减少LD诱导的肝胆结石形成并改善脂质代谢紊乱。结论  NXT629可能通过影响脂代谢相关基因表达改善肝胆结石。

       Objective  To explore the mechanism on NXT629 improves hepatolithiasis formation．Methods  C57BL/6J mice were fed either a regular diet or a lithogenic diet（LD），with the LD group receiving injections of PPAR-α inhibitor NXT629．Liver steatosis was analyzed via HE staining，hepatic lipid accumulation was detected by Oil Red O staining，and total cholesterol，triglycerides，phospholipids，total bile acids，cholesterol saturation index，low density lipoprotein cholesterol，and high density lipoprotein cholesterol levels in bile or serum were measured using assay kits．RT-qPCR was employed to determine the mRNA expression of ABCG5/8，CYP7A1，CYP7B1，PPAR-α，and ABCB11 in mouse liver tissues．Results  The results showed that NXT629 target PPAR-α to down-regulate the mRNA levels of ABCG5，ABCG8，and ABCB11 in the livers of LD-fed mice，while increasing the mRNA levels of CYP7A1 and CYP7B1，thereby  reducing LD-induced hepatolithiasis formation and improving lipid metabolism disorders．Conclusions  NXT629 can improve cholesterol gallstones by affecting the expression of genes related to lipid metabolism．