纤维介素2对糖尿病大鼠心功能及肝细胞生长因子/c-Met信号通路影响的观察

Effect of fibrinogen-like protein 2 to cardiac function and hepatocyte growth factor/c-Met signal pathway in diabetic rats

目的探讨纤维介素2(Fgl 2)对糖尿病大鼠心功能及肝细胞生长因子(HGF)/c-Met信号通路的影响。方法 SD大鼠建立糖尿病模型后,随机分为模型对照(Con)组、空白慢病毒载体(BLV)组、Fgl 2基因低表达慢病毒载体(Fgl 2)组,同时选择10只正常SD大鼠作为正常对照(NC)组。4组大鼠分别单次尾静脉注射生理盐水、空白慢病毒载体、Fgl 2基因低表达慢病毒载体(5×108IU/ml)及生理盐水4周后,检测各组FBG、TC、TG、HDL-C和LDL-C,采用多普勒彩超分析各组左心室舒张末期内径(LVIDd)、左心室收缩末期内径(LVIDs)、左室舒张末期室壁厚度(LVWTd)、左室收缩末期室壁厚度(LVWTs)、短轴缩短率(FS)和左心室射血分数(LVEF),分别采用RT-PCR和Westen blot测定各组心室肌Fgl 2、HGF和c-Met mRNA和蛋白的表达。结果 Con组、BLV组和Fgl 2组FBG、TC、TG、HDLC和LDL-C水平比较,差异均无统计学意义(P>0.05);Fgl 2组LVIDd、LVIDs、LVWTd和LVWTs较Con组或BLV组降低(P<0.05),FS和LVEF较Con组或BLV组升高(P<0.05);Fgl 2组心肌HGF和c-Met mRNA水平较Con组或BLV组升高(P<0.05),而Fgl 2mRNA水平较Con组和BLV组降低(P<0.05);Fgl 2组心肌HGF和c-Met蛋白水平较Con组和BLV组升高(P<0.05),而Fgl 2蛋白水平较Con组和BLV组降低(P<0.05)。结论慢病毒介导的Fgl 2基因低表达对糖尿病大鼠血糖及血脂无影响,但是可抑制心室重构,并且激活HGF/c-Met信号通路,从而对心脏起保护作用。

Objective To explore the effect of fibrinogen-like protein 2 （Fgl 2）to cardiac function and hepatocyte growth factor（HGF）/c-Met signal pathway in diabetic rats. Methods Rats were divided into model control （Con）group, blank lentiviral vector control （BLV）group and BLV group of Fgl 2 gene low expression （Fgl 2）after diabetic rat models were made. 10 normal rats were selected as normal control （NC） group. Normal saline, BLV, lentiviral vector of Fgl 2 gene low expression （5）〈 10^8IU/ml） and normal saline were respectively administered in the above four groups by single caudal vein injection. The levels of FBG,TC,TG, HDL-C,and LDL-C were determined after 4 weeks in each group. LVIDd,LVIDs, LVWTd, LVWTs, FS and LVEF by Colour Doppler ultrasonography were determined after 4 weeks in each group. The mRNA and protein expressions of Fgl 2, HGF and c-Met in myocardium were determined by Real-time PCR and Westen-blot. Results The levels of FBG, TC, TG, HDL-C and LDL-C were not significantly different among Con, BLV and Fgl 2 groups （P〉0.05）. LVIDd, LVIDs, LVWTd and LVWTs in Fgl 2 group were significantly decreased compared with those in Con and BLV group （P〈0.05） ,but FS and LVEF were significantly increased in Fgl 2 group （P〈0.05）. The mRNA levels of HGF and c-Met in Fgl 2 group were significantly increased than in Con and BLV group （P〈0.05）, but mRNA level of Fgl 2 was significantly decreased in Fgl 2 group （P〈0.05）. Protein levels of HGF and c- Met in Fgl 2 group were significantly increased compared with those in NC group and BLV group （P〈0.05） ,but protein level of Fgl 2 was significantly decreased in Fgl 2 group （P〈0.05）. Conclusion Fgl 2 gene low expression has no effect to blood glucose and lipids, but can protect heart by inhibiting the ventricular remodeling and activate the HGF/c-Met signal pathway.