脂联素干预对宫腔粘连大鼠子宫内膜组织中NLRP3、TGF-β1和Smad2表达的影响

Effects of adiponectin on expressions of NLRP3,TGF-β1 and Smad2 in uterine endometrium tissue of rats with intrauterine adhesion

目的:探讨脂联素干预对宫腔粘连大鼠子宫内膜组织中NLRP3、TGF-β1和Smad2表达的影响。方法:健康雌性SD大鼠24只采用双重损伤法建立宫腔粘连模型后,随机平均分为模型组(腹腔注射生理盐水1 mL/d)和脂联素组[腹腔注射脂联素蛋白10μg/(kg·d)+生理盐水1 mL/d],连续干预14 d;12只未造模大鼠为正常对照组。末次给药后,麻醉大鼠,收取子宫组织,HE染色及Masson染色法检测子宫内膜腺体数量和纤维化面积百分比,免疫组化、Western blot及RT-qPCR法检测NLRP3、TGF-β1及Smad2蛋白和mRNA的表达。结果:正常对照组、模型组和脂联素组子宫内膜腺体数分别为(55.1±5.6)、(13.8±4.5)和(33.7±7.8),纤维化面积百分比分别为(5.39±0.65)%、(65.18±1.92)%和(38.16±1.91)%;与正常对照组比较,模型组腺体数减少,纤维化面积百分比增加(P<0.05);与模型组比较,脂联素组腺体数增加,纤维化面积百分比减少(P<0.05)。模型组和脂联素组子宫内膜组织中NLRP3、TGF-β1和Smad2蛋白和mRNA的表达均高于正常对照组(P<0.05);脂联素组低于模型组(P<0.05)。结论:脂联素可能通过抑制NLRP3炎症小体的激活和TGF-β1/Smad2信号通路,减轻宫腔粘连大鼠子宫内膜炎症,从而抑制纤维化进展。

Aim:To explore the effects of adiponectin on the expressions of NLRP3,TGF-β1 and Smad2 in uterine endometrium tissue of rats with intrauterine adhesion.Methods:A total of 24 healthy female SD rats were used to establish intrauterine adhesion model by mechanical injury and infection,then were allocated into 2 groups(12 in each group),and were injected peritoneally with normal saline 1 mL/d(model group)or adiponectin 10μg/(kg·d)+normal saline 1 mL/d(adiponectin group)for 14 days,respectively.The other 12 rats without intervention were normal control.After the injection,rat uterine endometrium tissue samples were collected to detect the number of endometrial glands by HE staining,the percentage of endometrial fibrosis area by Masson staining,and the protein and mRNA expressions of NLRP3,TGF-β1 and Smad2 by IHC,Western blot and RT-qPCR.Results:The number of endometrial glands in normal control,model,and adiponectin groups was(55.1±5.6),(13.8±4.5),and(33.7±7.8),the percentage of endometrial fibrosis area was(5.39±0.65)%,(65.18±1.92)%and(38.16±1.91)%,respectively;compared with normal control group,the number of endometrial glands decreased,and the percentage of endometrial fibrosis area increased in model group(P<0.05);while compared with model group,the number of endometrial glands increased,and the percentage of endometrial fibrosis area decreased in adiponectin group(P<0.05).The protein and mRNA expressions of NLRP3,TGF-β1 and Smad2 were higher in model group and adiponectin group than those in normal control group(P<0.05),and those in adiponectin group were lower than those in model group(P<0.05).Conclusion:Adiponectin might reduce imflammation,so to inhibit fibrosis in rats with uterine adhesion through inhibiting NLRP3 inflammasome activation and TGF-β1/Smad2 signaling pathway.