丹参素通过STAT3/JAK2/SOCS1信号通路在妊娠期糖尿病干预中的作用机制研究

Mechanism of danshensu in gestational diabetes mellitus through STAT3/JAK2/SOCS1 signaling pathway

目的:探究不同剂量丹参素对妊娠期糖尿病模型大鼠肾脏的影响及对STAT3/JAK2/SOCS1信号通路分子的干预作用。方法:对SPF级怀孕SD大鼠进行链脲佐菌素(STZ)注射构建妊娠期糖尿病模型,将大鼠随机分为对照组(n=10)、模型组(n=10)、厄贝沙坦组(n=10),丹参素低剂量组(n=10)、丹参素中剂量组(n=10)和丹参素高剂量组(n=10),造模成功后各治疗组分别给予厄贝沙坦[10 mg/(kg·d)]及低[10 mg/(kg·d)、中[15 mg/(kg·d)]、高[20 mg/(kg·d)]剂量的丹参素灌胃7 d。HE染色观察肾脏组织病理变化;大生化检测血清肌酐(Scr)、血尿素氮(BUN)、尿蛋白,血糖仪检测空腹血糖,通过qPCR和Western blot检测肾脏组织中信号传感器和转录激活剂3 (STAT3)、酪氨酸蛋白激酶2 (JAK2)、抑制细胞因子信号1 (SOCS1)的mRNA和蛋白表达水平。结果:丹参素能显著降低妊娠期糖尿病大鼠肾脏损伤;降低外周血Scr、BUN、尿蛋白和空腹血糖水平,并且显著抑制STAT3、JAK2和SOCS1的mRNA和蛋白表达水平(均P<0.01)。结论:丹参素可以降低妊娠期糖尿病大鼠肾脏损伤,其机制可能与抑制STAT3/JAK2/SOCS1信号通路有关。

Objective:To explore the effect of different doses of danshensu on the kidneys of gestational diabetes model rats and its intervention on STAT3/JAK2/SOCS1 signaling pathway molecules.Methods:A model of gestational diabetes mellitus was established in SPF pregnant SD rats by STZ injection.The rats were randomly divided into control group(n=10),model group(n=10)and irbesartan group(n=10),danshensu low-dose group(n=10),danshensu medium-dose group(n=10)and danshensu high-dose group(n=10).After successful modeling,each treatment group was given irbesartan 10 mg/(kg·d)and low[10 mg/(kg·d)],medium[15 mg/(kg·d)]and high[20 mg/(kg·d)]doses of danshensu by gavage for 7 days.The pathological changes were detected in the kidney tissue of the rats in each group by HE staining.Serum creatinine(Scr),blood urea nitrogen(BUN),urine protein were detected by macrobiochemistry,fasting blood glucose was detected by blood glucose meter.Western blot and qPCR were used to detect signal transducer and activator of transcription 3(STAT3),Janus kinase 2(JAK2),suppressor of cytokine signaling 1(SOCS1)mRNA and protein expression levels.Results:Danshensu could significantly reduce kidney damage in gestational diabetes mellitus and decrease the levels of Scr,BUN,urine protein and fasting blood glucose in peripheral blood,and significantly inhibit the mRNA and protein expression levels of STAT3,JAK2 and SOCS1(all P<0.01).Conclusion:Danshensu can reduce kidney damage in gestational diabetic rats,and its mechanism may be related to the inhibition of STAT3/JAK2/SOCS1 signaling pathway.