胰高血糖素样肽-2调节去卵巢大鼠脂代谢的研究

Effect of Glucagon-Like Peptide2 on Lipid Metabolism of Ovariectomized Rats

目的研究胰高血糖素样肽-2对去卵巢大鼠脂代谢的调节作用。方法31只6月龄SD大鼠随机分为假手术组(sham,n=7)和去卵巢手术组(OVX,n=24)。OVX组进一步随机分为GLP-2干预组(OV+GLP-2,n=12)及安慰剂亚组(OV,n=12)。适应性喂养1w后进行假手术或双侧去卵巢手术,药物干预于术后第12周开始,持续4w,干预期间每周称取体质量。GLP-2干预组使用GLP-2(160 g/kg/d,皮下注射),OV组、sham组则皮下注射等量生理盐水(NS)。干预结束后,大鼠处死,采集血液,制备血清,并检测空腹血糖、血清TG、T-CHO、LDL-C、HDL-C浓度、及胰岛素水平,计算HOMA-IR和HOMA-β。取大鼠肝脏用qRT-PCR方法检测GLUT4、PPAR-γ、Fas、CPT-1、HMGR、LDLR、EsR、SR-B1mRNA水平。结果接受去卵巢手术的两组GLP-2组与OV组体质量上升与sham组比较,差异有统计学意义(P<0.01)。GLP-2干预后,OV组和OV+GLP-2组相比,体质量差异有统计学意义(P>0.05)。OV组与sham组相比TG,T-CHO,LDL-C水平升高,差异有统计学意义(P<0.05或P<0.01),HDL-C水平略下降,但差异无统计学意义(P>0.05)。在GLP-2干预后,相较于OV组,GLP-2组T-CHO,LDL-C水平下降,差异有统计学意义(P<0.01),HDL-C水平上升(P<0.05),TG水平差异无统计学意义(P>0.05)。去卵巢手术后空腹血糖及胰岛素水平均升高,差异有统计学意义(P<0.05);GLP-2干预后空腹血糖降低,差异有统计学意义(P<0.05),胰岛素水平变化无统计学差异(P>0.05),HOMA-IR降低,HOMA-升高差异有统计学意义(P<0.05),qRT-PCR显示GLP-2干预后,CPT-1、HMGR、PPAR-γ,GLUT4、LDLR、EsR、SR-B1的mRNA水平升高,差异有统计学意义(P<0.05)。结论GLP-2对绝经后去卵巢大鼠的体质量、TG及雌激素水平影响无统计学意义,但可降低去卵巢大鼠的T-CHO、LDLC水平,升高HDL-C水平、改善胰岛素抵抗,并能从mRNA水平改善去卵巢大鼠的脂代谢。

Objective To explore the effect of glucagon-like peptide2(GLP-2)on lipid metabolism of the ovariectomized rats.Methods 31 6-month-old SDrats were randomly divided into 2 groups:shamgroup(n=7)and ovariectomized(OVX)group(n=24),and OVX group was further divided into 2 sub-groups:OVX+GLP-2 subgroup(n=12)and OV group(OVX+placebo,n=12);sham-operation or bilateral ovariectomy was performed on the rats 1week after adaptive feeding;drug intervention began at the12th week after surgery and kept on for 4 weeks;during the intervention,mass weight of the rats was recorded;GLP-2(160 g/kg/d,subcutaneous injection)was made to rats in OVX+GLP-2 subgroup while same volume of normal saline to rats in OVgroup and shamgroup;after intervention,the rats were sacrificed,blood samples collected and testing serums prepared;the levels of fasting blood glucose(FBG),serum TG,T-CHO,LDL-C,HDL-C concentration and insulin were detected and the values of HOMA-IR and HOMA-βwere calculated;qRT-PCR was applied in detecting the levels of GLUT4,PPAR-γ,Fas,CPT-1,HMGR,LDLR,EsR,SR-B1mRNA in rat liver.Results The weights of the rats in GLP-2 group and OVgroup after ovariectomy grewup much more than that in shamgroup(P<0.01);after the intervention of GLP-2,the difference in weight between OV group and OV+GLP-2 group was of no statistical significance(P>0.05);the levels of TG,T-CHO and LDL-C in OV group were higher than those in shamgroup with statistical difference(P<0.05)while the level of HDL-C in OV group was slightly lower than that in sham group but with no statistical difference(P>0.05);after the intervention of GLP-2,the levels of T-CHO and LDL-C in GLP-2 group were lower than those in OV group but with no statistical difference(P>0.01)while the level of HDL-C was higher than that in OV group with statistical difference(P<0.05),and no statistical difference was found in TG between GLP-2 group and OV group(P>0.05);the levels of FBGand insulin in OVX group were higher after ovariectomy than those before ovariectomy(P<0.05);a decrease was found in the level of FBG after the intervention of GLP-2(P<0.05)but no decrease of statistical significance was found in the level of insulin(P>0.05),and the level of HOMA-IR decreased and the level of HOMA-increased,both P<0.05;qRT-PCR indicated that the mRNA levels of CPT-1,HMGR,PPAR-γ,GLUT4,LDLR,EsR and SR-B1 all increased(all P<0.05).Conclusions GLP-2 is of no statistical influence on the weight and levels of TG and estrogen of ovariectomized rats while it can decrease the levels of T-CHO and LDL-C,raise the level of HDL-C,improve the insulin resistance and promote the lipid metabolism of ovariectomized rats in mRNA level.