利拉鲁肽对糖尿病大鼠心肌损伤的改善作用研究

Alleviates effect of the liraglutide on the diabetic cardiomyopathy in rats

目的观察利拉鲁肽(LRG)能否通过调控NOD样受体家族3(NLRP3)炎性小体延缓2型糖尿病(T2DM)大鼠心肌病变及其机制。方法按照体重将大鼠随机分为3组:正常组、模型组和实验组,每组10只。实验组皮下注射LRG 200μg·kg ^-1,正常组和模型组给予等剂量0.9%NaCl,1次/日,连续4周。以试剂盒法测定肌酸激酶(CK)和乳酸脱氢酶(LDH)水平;计算心脏质量指数(HMI)、左心室质量指数(LVWI);以免疫印迹法测定心肌组织NLRP3和沉默信息调节因子1(SIRT1)蛋白表达水平(灰度值)。结果正常组、模型组和实验组CK分别为(370.85±38.73),(615.12±52.57)和(493.49±45.32)U·mL^-1;这3组的LDH分别为(686.12±63.05),(1161.60±154.05)和(885.53±109.62)U·L^-1;这3组的HMI分别为(2.22±0.25),(3.04±0.16)和(2.51±0.25)mg·g^-1;这3组的LVWI分别为(1.59±0.18),(2.24±0.16)和(1.85±0.26)mg·g^-1;这3组的NLRP3蛋白表达分别为0.31±0.05,0.81±0.05和0.55±0.11;这3组的SIRT1蛋白表达分别为0.70±0.10,0.21±0.03和0.49±0.05;上述指标:模型组与正常组相比,差异均有统计学意义(均P<0.01);实验组与模型组相比,差异均有统计学意义(均P<0.01)。结论 LRG能够延缓T2DM心肌病变,其机制可能与激活SIRT1从而抑制NLRP3炎性小体的活化及减轻心肌炎性损伤有关。

Objective To investigate the effect of liraglutide(LRG)on the expression of NLR pyrin domain containing(NLRP3)in heart tissues of type 2 diabetes mellitus(T2DM)rats and its mechanisms.Methods SD rats were randomly divided into three groups according by weight:normal group,model group and experimental group,with 10 rats in each group.The experimental group was given subcutaneous injection of 200 μg·kg^ -1 LRG;normal group and model group were given the equivalent volume of normal saline,1 times a day,for consecutive 4 weeks.Creatine kinase(CK)and lactate dehydrogenase(LDH) levels were measured by kits.Heart weight/body weight(HMI)and left ventricular weight/body weight(LVWI)were calculated.The protein expression levels(grey va-lue) of NLRP3,silent information regulator 1(SIRT1)in heart tissue were detected by Western-blot.Results The CK contents in normal group,model group and experimental group were(370.85±38.73),(615.12±52.57),(493.49±45.32)U·mL^ -1;the LDH in the three groups were (686. 12 ± 63. 05),(1161. 60 ± 154. 05),(885. 53 ± 109. 62) U·L^-1;HMI in the three groups were(2. 22 ± 0. 25),(3. 04 ± 0. 16),(2. 51 ± 0. 25) mg · g^-1;LVWI in the three groups were(1. 59 ± 0. 18),(2. 24 ± 0. 16),(1. 85 ± 0. 26) mg·g^-1;the protein expression of NLRP3 were 0. 31 ± 0. 05,0. 81 ± 0. 05,0. 55 ± 0. 11;the protein expression of SIRT1 were 0. 70 ± 0. 10,0. 21 ± 0. 03,0. 49 ± 0. 05. Comparison between model group and normal group,the difference of the factors were significantly(all P < 0. 01);comparison between experimental group and model group,the difference of the factors were significantly(all P < 0. 01). Conclusion LRG protects against myocardial injury in T2DM rats by inhibiting the NLRP3 inflammatory body activation and alleviating myocardial inflammatory injury through the activation of SIRT1.