Many studies indicate that gallstone formation has genetic components. The abnormal expression of lipid-related genes could be the basis for particular forms of cholesterol gallstone disease. The aim of this study was to obtain insight into lipid metabolism disorder during cholesterol gallstone formation and to evaluate the effect of ursodeoxycholic acid (UDCA) on the improvement of bile lithogenicity and its potential influence on the transcription of lipid-related genes. Gallstone-susceptible mouse models were induced by feeding with a lithogenic diet (LD) for 8 weeks. Bile and liver tissues were obtained from these mouse models after 0, 4 and 8 weeks. Bile lipids were measured enzymatically, and the cholesterol saturation index (CSI) was calculated to evaluate the bile lithogenicity by using Carey’s critical tables. Real-time polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of farnesoid X receptor (FXR), liver X receptor (LXR), adenosine triphosphate-binding cassette subfamily G member 5/8 (ABCG5/8), cholesterol 7-α hydroxylase (CYP7A1), oxysterol 7-α hydroxylase (CYP7B1), sterol 27-α hydroxylase (CYP27A1), peroxisome proliferator-activated receptor alpha (PPAR-α) and adenosine triphosphate-binding cassette subfamily B member 11 (ABCB11). The rate of gallstone formation was 100% in the 4-week group but only 30% in the UDCA-treated group. The UDCA-treated group had a significantly lower CSI compared with other groups. Of special note, the data on the effects of UDCA showed higher expression levels of ABCG8, ABCB11 and CYP27A1, as well as lower expression levels of LXR and PPAR-α, compared to the model control group. UDCA exhibits tremendously potent activity in restraining lipid accumulation, thus reversing the lithogenic effect and protecting hepatocytes from serious pathological damage. The abnormal expression of ABCG8, CYP7A1, CYP27A1, LXR and PPAR-α might lead to high lithogenicity of bile. These results are helpful in exploring new lipid metabolism pathways and potential targets for the treatment of cholesterol stones and for providing some basis for the study of the pathogenesis and genetic characteristics of cholelithiasis. Research on the mechanism of UDCA in improving lipid metabolism and bile lithogenicity may be helpful for clinical treatment and for reducing the incidence of gallstones.

中文翻译：

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熊去氧胆酸对小鼠胆固醇胆结石模型脂质代谢基因相对表达的影响。

许多研究表明胆结石的形成具有遗传成分。脂质相关基因的异常表达可能是特定形式的胆固醇胆结石病的基础。这项研究的目的是了解胆固醇胆结石形成过程中的脂质代谢紊乱，并评估熊去氧胆酸（UDCA）对改善胆汁石原性的作用及其对脂质相关基因转录的潜在影响。胆石易感小鼠模型是通过饲喂石原性饮食（LD）8周而诱发的。在0、4和8周后从这些小鼠模型获得胆汁和肝组织。酶法测定胆汁脂质，并使用Carey临界表计算胆固醇饱和指数（CSI）以评估胆汁的致石性。使用实时聚合酶链反应（RT-PCR）检测法呢素X受体（FXR），肝X受体（LXR），三磷酸腺苷结合盒亚家族G成员5/8（ABCG5 / 8）的mRNA表达水平，胆固醇7-α羟化酶（CYP7A1），氧固醇7-α羟化酶（CYP7B1），固醇27-α羟化酶（CYP27A1），过氧化物酶体增殖物激活受体α（PPAR-α）和三磷酸腺苷结合盒B亚家族11（ ABCB11）。在4周组中胆结石形成率为100％，而在UDCA治疗组中只有30％。与其他组相比，UDCA治疗组的CSI显着降低。特别值得注意的是，与模型对照组相比，有关UDCA影响的数据显示ABCG8，ABCB11和CYP27A1的表达水平较高，而LXR和PPAR-α的表达水平较低。UDCA在抑制脂质蓄积方面显示出极大的活性，从而逆转了岩性作用并保护了肝细胞免受严重的病理损害。ABCG8，CYP7A1，CYP27A1，LXR和PPAR-α的异常表达可能导致胆汁的高致卵性。这些结果有助于探索新的脂质代谢途径和治疗胆固醇结石的潜在靶标，并为研究胆石症的发病机理和遗传特征提供一些依据。研究UDCA改善脂质代谢和胆石形成性的机制可能有助于临床治疗和减少胆结石的发生。ABCG8，CYP7A1，CYP27A1，LXR和PPAR-α的异常表达可能导致胆汁的高致卵性。这些结果有助于探索新的脂质代谢途径和治疗胆固醇结石的潜在靶标，并为胆石症的发病机理和遗传特征的研究提供基础。研究UDCA改善脂质代谢和胆结石性的机制可能有助于临床治疗和减少胆结石的发生。ABCG8，CYP7A1，CYP27A1，LXR和PPAR-α的异常表达可能导致胆汁的高致卵性。这些结果有助于探索新的脂质代谢途径和治疗胆固醇结石的潜在靶标，并为胆石症的发病机理和遗传特征的研究提供基础。研究UDCA改善脂质代谢和胆石形成性的机制可能有助于临床治疗和减少胆结石的发生。这些结果有助于探索新的脂质代谢途径和治疗胆固醇结石的潜在靶标，并为研究胆石症的发病机理和遗传特征提供一些依据。研究UDCA改善脂质代谢和胆石形成性的机制可能有助于临床治疗和减少胆结石的发生。这些结果有助于探索新的脂质代谢途径和治疗胆固醇结石的潜在靶标，并为胆石症的发病机理和遗传特征的研究提供基础。研究UDCA改善脂质代谢和胆石形成性的机制可能有助于临床治疗和减少胆结石的发生。