骨桥蛋白对小鼠胆囊结石形成的 作用及其机制探讨

Effect of osteopontin on gallstone formation in mice and its mechanism

摘要:

目的 研究骨桥蛋白（OPN ）基因敲除对小鼠胆囊结石形成的影响及其作用机制。方法 选取 7 只OPN 基因敲除小鼠和7 只C57BL/6J 普通小鼠致石饮食喂养8 周，分别作为敲除组和对照组。观察两组 小鼠胆结石形成率，检测胆汁胆固醇含量、ATP 结合盒转运子G 亚家族成员5（ABCG5）、ABCG8 mRNA 和蛋白在胆囊组织中的表达。结果 敲除组小鼠结石形成率（14.29%）低于对照组（85.71%）（P <0.05）。敲 除组小鼠胆汁胆固醇含量（5.35±1.08）低于对照组（9.34+0.85）（P <0.05）。敲除组小鼠ABCG5、ABCG8 mRNA 和蛋白表达水平低于对照组（P <0.05）。结论 OPN 基因敲除小鼠胆结石形成率较普通小鼠低，可能 与OPN 敲除后胆囊胆固醇转运蛋白ABCG5、ABCG8 表达受抑制，导致胆囊胆汁中胆固醇含量降低有关。

Abstract:

Objective To study the effect of osteopontin (OPN) gene knockout on gallstone formation in mice and the mechanism. Methods In this study 7 OPN knockout mice (OPN knockout group) and 7 C57BL/6J mice (control group) were fed with lithogenic diet for 8 weeks. Then gallstone formation rate, bile cholesterol concentration, and mRNA and protein expressions of ATP binding cassette transporter subfamily G member 5 and 8 (ABCG5 and ABCG8) in gallbladder tissue were observed. Results The stone formation rate of the OPN knockout group was significantly lower than that in the control group (14.29 vs . 85.71%), the difference was statistically significant (P < 0.05). The bile cholesterol concentration in the OPN knockout group was significantly lower than that in the control group [(5.35 ± 1.08) vs . (9.34 ± 0.85)], the difference was statistically significant (P < 0.05). The expressions of ABCG5 and ABCG8 mRNAs and proteins in the OPN knockout group were significantly lower than those in the control group (P < 0.05). Conclusions The phenomenon that gallstone formation rate in OPN knockout mice was lower than that in normal mice, may be related to decrease of cholesterol transporters ABCG5 and ABCG8 in gallbladder tissue which results in lower cholesterol concentration in gallbladder bile.