可溶性mB7-H4对ConA诱导小鼠肝损伤的保护作用

目的: 探讨可溶性mB7-H4蛋白对肝脏的免疫性损伤的保护作用,阐明其作用机制。 方法: 采用异丙基硫代半乳糖苷(IPTG)诱导pET/mB7-H4表达,通过纯化、复性以及去除内毒素,获得具有生物活性的可溶性mB7-H4蛋白。小鼠随机分为对照(生理盐水)组、Con A组和mB7-H4蛋白100、200及400 μg组,除对照组外其余各组小鼠通过尾静脉注射Con A建立肝损伤模型(mB7-H4蛋白组小鼠在注射Con A前2 h和注射后8 h分2次给予mB7-H4蛋白),并于注射Con A后24和48 h,摘取各组小鼠眼球取血及引颈处死取肝脏,分离血清,检测天冬氨酸氨基转移酶(ALT)、丙氨酸氨基转移酶(AST)、白细胞介素4(IL-4)和γ干扰素(IFN-γ)水平,并检测肝脏组织病理学变化。 结果: 与对照组比较,其他各组小鼠血清ALT、AST、IL-4和IFN-γ水平较均明显升高(P<0.05);与Con A组比较,mB7-H4蛋白组小鼠血清ALT、AST、IL-4和IFN-γ水平均明显降低(P<0.05或 P<0.01)。HE染色,mB7-H4蛋白组小鼠肝脏损伤均较Con A组有不同程度的减轻。 结论: 可溶性mB7-H4蛋白对Con A诱导的肝脏免疫性损伤具有保护作用,可能是通过抑制IL-4和IFN-γ的产生和(或)分泌而发挥作用。

Protective effect of soluble protein mB7-H4 on liver injury of mice induced by Con A

Objective: To explore the protective effect of soluble protein B7-H4 on the immune liver injury, and to clarify its action mechanism.Methods: The isopropyl glucosinolate galactose glucoside (IPTG)was used to induce the expression of pET/mB7-H4.Through purification and renaturation and removing endotoxin,bioactive soluble mB7-H4 protein was obtained. The mice were randomly divided into normal saline (control)group,Con A group,100 μg mB7-H4 protein group,200 μg mB7-H4 protein group and 400 μg mB7-H4 protein group.The mice in all groups except control group were injected with Con A by tail vein to establish liver injury models.By tail intravenous injection,the mice in 100 μg mB7-H4 protein group,200 μg mB7-H4 protein group and 400 μg mB7-H4 protein group were injected with 50,100 and 200 μg soluble mB7-H4protein 2 h before ConA injection and 8 h after Con A injection. 24 and 48 h after injection of Con A,the eyeball blood of the mice was collected and the liver was obtained after the mice was killed;the levels of serum aspartate aminotransferase (ALT),alanine aminotransferase (AST),interleukin 4 (IL-4)and gamma interferon (IFN-γ)of the mice were detected. The pathological changes the liver tissue were determined.Results: Compared with control group,the levels of serum ALT,AST,IL-4 and IFN-γ of the mice in other groups were significantly increased(P<0.05). Compared with Con A group,the levels of serum ALT,AST,IL-4 and IFN-γ of the mice in mB7-H4 protein groups were significantly decreased(P<0.05 or P<0.01). The HE staining results showed that the liver injury degree in mBT-H4 protein groups is improved compared with Con A group. Conclusion: The soluble B7-H4 protein has protective effect on the immune injury of liver induced by Con A by inhibiting the secretion of IL-4 and IFN-γ.