丹参提取物对甲状腺功能亢进模型大鼠心脏缺血再灌注损伤的保护作用及对NLRP3/Caspase-1通路的影响

The protective effect of Salvia extract on the re-injury of the heart in hyperthyroidism rats and its influence on NLRP3/Caspase-1 pathway

目的探讨丹参提取物对甲状腺功能亢进模型大鼠心脏缺血再灌注损伤(I/R)的保护作用及对NLRP/Caspase-1通路的影响。方法采用左旋甲状腺素灌胃及冠状动脉结扎建立大鼠甲状腺功能亢进心脏I/R损伤模型,随机分为模型对照组、丙硫氧嘧啶组和丹参提取物低、高剂量组,并设立正常对照组。给药4周后,超声诊断仪测定FS、LVIDs、LVIDd、EF水平;全自动生化仪测定FT3、FT4、TSH水平;RT-PCR法及western-blot法测定心脏NLRP3、Caspase-1水平。结果与正常组比较,模型组LVIDd、LVIDs水平升高,FS、EF水平降低(均P<0.01);与模型组比较,丙硫氧嘧啶组和丹参提取物低、高剂量组LVIDd、LVIDs水平降低,FS、EF水平升高(均P<0.01);与丙硫氧嘧啶组比较,丹参提取物低、高剂量组LVIDd、LVIDs水平升高,FS、EF水平降低(均P<0.01);丹参提取物高剂量组LVIDd、LVIDs水平低于丹参提取物低剂量组,FS、EF水平高于丹参提取物低剂量组(均P<0.01)。与正常组比较,模型组FT3、FT4水平升高,TSH水平降低(均P<0.01);与模型组比较,丙硫氧嘧啶组和丹参提取物低、高剂量组FT3、FT4水平降低,TSH水平升高(均P<0.01);与丙硫氧嘧啶组比较,丹参提取物低、高剂量组FT3、FT4水平升高,TSH水平降低(均P<0.01);丹参提取物高剂量组FT3、FT4水平低于丹参提取物低剂量组,TSH水平高于丹参提取物低剂量组(P<0.01)。与正常组比较,模型组NLRP3 m RNA、Caspase-1 mRNA蛋白水平升高(均P<0.01);与模型组比较,丙硫氧嘧啶组和丹参提取物低、高剂量组NLRP3 m RNA、Caspase-1 m RNA蛋白水平降低(均P<0.01);与丙硫氧嘧啶组比较,丹参提取物低、高剂量组NLRP3 m RNA、Caspase-1 mRNA蛋白水平升高(均P<0.01);丹参提取物高剂量组NLRP3 mRNA、Caspase-1 m RNA蛋白水平低于丹参提取物低剂量组(均P<0.01)。结论丹参提取物对甲状腺功能亢进心脏I/R损伤具有明显保护作用,其机制可能与丹参提取物抑制甲状腺功能亢进心脏I/R损伤大鼠心脏NLRP3/Caspase-1通路的激活有关。

Objective To explore the protective effect of Salvia extract on rat heart ischemia-reperfusion injury caused by hyperthyroidism and its influence on NLRP/Caspase-1 pathway. Methods Gavage of levothyroxine and coronary artery ligation were used to establish a rat model of hyperthyroidism with cardiac ischemia-reperfusion injury. The rats were randomlydivided into model group,propylthiouracil group,low-dose Salvia extract group,high-dose Salvia extract group and normal control group. Four weeks after administration,the ultrasound diagnostic instrument measured FS,LVIDs,LVIDd,and EF;biochemical instrument measured FT3,FT4,TSH levels;RT-PCR method and western-blot method measured cardiac NLRP3 and Caspase-1 levels. Results Compared with normal group,the levels of LVIDd,LVIDs in model group were higher(P<0.01),and the levels of TSH,FS,and EF were lower(P<0.01);compared with model group,the levels of LVIDd,LVIDs in propylthiouracil group and low and high-dose Salvia extract groups were lower(P<0.01);compard with propylthiouracil group,the levels of LVIDd,LVIDs in low and high-dose Salvia extract groups were increased,and the levels of FS,EF were reduced(P<0.01);compared with normal group,the levels of FT3 and FT4 in model group were higher,and the level of TSH were lower(P<0.01)and the levels of FT3 and FT4 in high-dose Salvia extract group were lower than those in low-dose Salvia extract group,the level of TSH was higher than low-dose Salvia extract group(P<0.01);compared with propylthiouracil group,the levels of NLRP3 m RNA and Caspase-1 m RNA in low and high-dose Salvia extract groups were lower,the level of m RNA and protein were higher(P<0.01),and the levels of NLRP3 m RN,Caspase-1 m RNA protein in high-dose high-dose Salvia extract group were lower than those in low-dose Salvia extract group. Conclusion Salvia extract has a significant protective effect on cardiac I/R injury in hyperthyroidism;its mechanism maybe related to the inhibition of Salvia extract on the activation of NLRP3/Caspase-1 pathway in the heart of hyperthyroid I/R rats.