低铅染毒促进非酒精性脂肪性肝病大鼠 Hcy 升高的分子机制研究

The molecular mechanisms of low lead exposure promoting Hcy increase in rats with nonalcoholic fatty liver disease

摘要:

目的 研究低铅染毒对非酒精性脂肪性肝病大鼠同型半胱氨酸（Hcy）升高的分子机制。方法 将 40 只SD 大鼠分为普通饲料组、低铅染毒普通饲料组、高脂饲料组及低铅染毒高脂饲料组，每组10 只。喂养 8 周后处死，检测大鼠血清肝功能、肝铅、血铅、血清Hcy、血清炎症因子和肝脏MTHFR、MTR 及CBS 蛋 白和mRNA 的表达。结果 普通饲料组和低铅染毒普通饲料组肝脏切片正常，高脂饲料组和低铅染毒高脂饲 料组有明显脂肪空泡，低铅染毒普通饲料组和低铅染毒高脂饲料组血铅和肝铅含量高于普通饲料组（P <0.05）， 低铅染毒高脂饲料组血铅和肝铅含量高于低铅染毒普通饲料组和高脂饲料组（P <0.05）。低铅染毒普通饲料 组、高脂饲料组和低铅染毒高脂饲料组肝功能指标均高于普通饲料组（P <0.05），高脂饲料组和低铅染毒高 脂饲料组肝功能指标高于低铅染毒普通饲料组（P <0.05），低铅染毒高脂饲料组肝功能指标高于高脂饲料组 （P <0.05）。高脂饲料组和低铅染毒高脂饲料组Hcy 高于普通饲料组和低铅染毒普通饲料组（P <0.05），叶酸 和维生素B12 低于普通饲料组和低铅染毒普通饲料组（P <0.05）；低铅染毒高脂饲料组Hcy 高于高脂饲料组 （P <0.05），叶酸和维生素B12 低于高脂饲料组（P <0.05）。高脂饲料组和低铅染毒高脂饲料组炎症因子高于普 通饲料组和低铅染毒普通饲料组（P <0.05），低铅染毒高脂饲料组高于高脂饲料组（P <0.05）。高脂饲料组和 低铅染毒高脂饲料组MTHFR 蛋白和mRNA 相对表达量低于普通饲料组（P <0.05），低铅染毒高脂饲料组 MTHFR 蛋白和mRNA 相对表达量低于高脂饲料组（P <0.05）。结论 在高脂饲料喂养的同时给予醋酸铅慢 性染毒，可促进血清Hcy 升高，这可能与低铅染毒可进一步抑制肝脏MTHFR 表达有关。

Abstract:

Objective To study the molecular mechanism of low lead exposure promoting elevation of homocysteine (Hcy) in rats with nonalcoholic fatty liver disease. Methods Forty SD rats were divided into the normal diet group, low lead exposure normal diet group, high fat diet group and low lead exposure high fat diet group. After 8 weeks, all rats were sacrificed. Liver function, liver and blood lead, serum Hcy, inflammatory factors, MTHFR, MTR and CBS protein and mRNA expression of liver were detected. Results The liver sections were normal in normal diet group and low lead exposure normal diet group, and had obvious fat vacuoles in high fat diet group and low lead exposure high fat diet group; the blood lead and liver lead in the low lead exposure normal diet group and low lead exposure high fat feed group were higher than those in the normal diet group, and those in low lead exposure high fat diet group were higher than those in low lead exposure normal diet group and high fat diet group (P < 0 05). The AST, ALT, Hcy, IL-1α, IL-1β, IL-6 and TNF-α in the low lead exposure normal diet group, high fat diet group and low lead exposure high fat diet group were higher than those in the normal diet group (P < 0.05), and folic acid and vitamin B12 were lower than those in the low lead exposure group (P < 0.05); the AST, ALT, Hcy, IL-1α, IL-1β, IL-6 and TNF-α in the low lead exposure high fat diet group was were higher than those in the low lead exposure normal diet group (P < 0.05), and folic acid and vitamin B12 were lower than them in the low lead exposure normal feed group (P < 0.05); the AST and ALT in high fat diet group and low lead exposure high fat diet group were higher than those in the low lead exposure common diet group (P < 0.05); the AST and ALT in low lead exposure high fat diet group were higher than those in the high fat diet group (P < 0.05). The MTHFR proteins and mRNA expression in the high-fat diet group and the low lead high-fat diet group were significantly lower than those in the normal diet group (P < 0.05), and those in the low-lead exposure high-fat diet group were significantly lower than those in the high-fat diet group (P < 0.05). Conclusions Low lead exposure can promote the increase of serum Hcy while high-fat feed, which may be related with it can reduced the expression of MTHFR in liver.