甲硫氨酸维生素B_1对妊娠期肝内胆汁淤积症模型大鼠的治疗作用

Role of methionine and vitamin B_1 for injection in the treatment of intrahepatic cholestasis in pregnant rats

目的探讨甲硫氨酸维生素B1针(甲维比)对妊娠期肝内胆汗淤积症(intrahepatic cholestasis of pregnancy,ICP)模型大鼠的治疗作用。方法妊娠大鼠48只,随机分为正常妊娠组、模型组、甲维比高剂量组2ml/(kg.d)、甲维比中剂量组1ml/(kg.d)、甲维比低剂量组0.5ml/(kg.d)、腺苷蛋氨酸组100mg/(kg.d)。从其妊娠第12天开始肌内注射苯甲酸雌二醇2.5mg/(kg.d),连续6d,同时给药1周。正常妊娠组与模型组均肌注等容积蒸馏水。检测大鼠血清总胆红素(TBIL)、丙氨酸氨基转移酶(ALT)、总胆汁酸(TBA)、雌二醇(E2)水平;并比较各组大鼠肝脏组织病理变化;运用免疫组化法测定大鼠肝组织Th1细胞因子及核因子NF-κB的表达。结果甲维比高、中剂量治疗组及腺苷蛋氨酸组均较模型组大鼠流产率、胚胎致死率显著降低(P<0.01),大鼠血清TBIL、ALT、TBA、E2水平也降低(P<0.01),Th1细胞因子及核因子NF-κB的表达下调(P<0.01),大鼠的肝脏病理变化得到较大改善。结论甲维比可通过降低模型大鼠肝组织Th1细胞因子及核因子NF-κB的表达对ICP模型大鼠发挥明显的治疗作用。

Objective To explore the therapeutic effects of methionine and vitamin B1 for injection on intrahepatic cholestasis in pregnant rats and its nosogenesis.Methods Forty-eight rats in pregnancy were divided into 6 groups at random：normal group,model group,methionine and vitamin B1 high,middle and low dosage groups,S-adenosyl-L-methionine group.Rats were intramuscularly injected with 2.5 mg/（kg·d）estradiol benzoate for 6 days from the 12th day after pregnancy,meanwhile rats were given medicine for 1 week at the same time in treatment groups,while in normal group and model group the rats were intramuscularly injected with the same volume of distilled water.The serum levels of total bilirubin（TBIL）,ALT,total bile acid（TBA）,estradiol（E2）were detected,and the pathological changes of rat liver were observed and compared.Using immunohistochemical assay the expression of Th1 cytokine and NF-κB in rat liver was determined.Results Compared with model group,the abortion rate and embryonic death rate decreased in high and middle dosage groups（P〈0.01）,the levels of TBIL,ALT,TBA,E2 and the expression of NF-κB also decreased（P〈0.01）,and liver pathological changes were ameliorated.Conclusion Methionine and vitamin B1 for injection has obvious therapeutic effects on intrabeparic cholestasis in pregnant rats by down-regulating the expression of NF-κB and Th1 cytokine.