粉防己碱调节Toll样受体4/核因子-kB通路在子痫前期大鼠模型中的影响

Effects of tetrandrine on the regulating Toll-like receptor 4/nuclear factor-κB pathway in the preeclampsia rat model

目的探究粉防己碱(Tet)调节Toll样受体4(TLR4)/核因子(NF)-κB通路对子痫前期(PE)大鼠模型的影响。方法20只SPF级Wistar雄性大鼠,40只雌性大鼠,进行PE大鼠建模,将20只妊娠大鼠随机分为两组,即A组与B组,每组10只;A组分为PE-1组与PE+Tet-1组,每组5只;B组分为PE-2组与PE+Tet-2组,每组5只。比较PE+Tet-1组与PE-1组、PE+Tet-2组与PE-2组妊娠各时间点血压、尿蛋白及胎盘重量、胎鼠重量、炎症因子、TLR4和NF-κB蛋白表达。结果妊娠第10天,PE+Tet-1组与PE-1组血压比较差异无统计学意义;妊娠第15、20天,PE+Tet-1组血压均低于PE-1组,差异有统计学意义(P<0.05)。妊娠第10、15天,PE+Tet-2组与PE-2组血压比较差异无统计学意义;妊娠第20天,PE+Tet-2组血压低于PE-2组,差异有统计学意义(P<0.05)。妊娠第10天,PE+Tet-1组与PE-1组24 h尿蛋白水平比较差异无统计学意义;妊娠第15、20天,PE+Tet-1组24 h尿蛋白水平均低于PE-1组,差异有统计学意义(P<0.05)。妊娠第10、15、20天,PE+Tet-2组与PE-2组24 h尿蛋白水平比较差异无统计学意义。PE+Tet-1组胎盘和胎鼠重量均大于PE-1组,差异有统计学意义(P<0.05);PE+Tet-2组胎盘和胎鼠重量均大于PE-2组,差异有统计学意义(P<0.05)。PE+Tet-1组IL-6、TNF-α水平均低于PE-1组,差异有统计学意义(P<0.05);PE+Tet-2组IL-6和TNF-α水平均低于PE-2组,差异有统计学意义(P<0.05)。PE+Tet-1组TLR4和NF-κB蛋白水平均明显低于PE-1组,差异有统计学意义(P<0.05);PE+Tet-2组TLR4和NF-κB蛋白水平均明显低于PE-2组,差异有统计学意义(P<0.05)。结论Tet调节TLR4/NF-κB通路对PE大鼠模型,可降低PE模型大鼠的血压,减少24 h尿蛋白,增加胎盘和胎鼠质量,促进胎鼠发育,抑制炎症因子的表达。

Objective To explore the effect of tetrandrine(Tet)regulating Toll-like receptor 4(TLR4)/nuclear factor(NF)pathway on preeclampsia(PE)rat models.Methods 20 SPF Wistar male rats and 40 female rats were used for PE rat modeling,20 pregnant rats were randomly divided into two groups,namely the group A and the group B,with 10 rats in each group;the group A was divided into the PE-1 group and the PE+Tet-1 group,with 5 rats in each group;the group B was divided into the PE-2 group and the PE+Tet-2 group,with 5 rats in each group.The blood pressure,urine protein and placental weight,fetal weight,inflammatory factors,TLR4 and NF-κB protein expression were compared between the PE+Tet-1 group and the PE-1 group,the PE+Tet-2 group and the PE-2 group at each time point of pregnancy.Results On the 10th day of pregnancy,there was no significant difference in blood pressure between the PE+Tet-1 group and the PE-1 group;on the 15th and 20th d of pregnancy,the blood pressure in the PE+Tet-1 group was lower than that in the PE-1 group,and the difference was statistically significant(P<0.05).On the 10th and 15th day of pregnancy,there was no significant difference in blood pressure between the PE+Tet-2 group and the PE-2 group;on the 20 th day of pregnancy,the blood pressure of the PE+Tet-2 group was lower than that of the PE-2 group,and the difference was statistically significant(P<0.05).On the 10 th day of pregnancy,there was no significant difference in 24 h urine protein level between the PE+Tet-1 group and the PE-1 group;on the 15th and 20th day of pregnancy,the 24 h urine protein level in the PE+Tet-1 group was lower than that in the PE-1 group,and the difference was statistically significant(P<0.05).On the 10th,15th and 20th day of pregnancy,there was no significant difference in 24 h urine protein level between the PE+Tet-2 group and PE-2 group.The weight of placenta and fetal rats in the PE+Tet-1 group was higher than that in the PE-1 group,and the difference was statistically significant(P<0.05);the weight of placenta and fetal rats in the PE+Tet-2 group was higher than that in the PE-2 group,and the difference was statistically significant(P<0.05).The levels of IL-6 and TNF-αin the PE+Tet-1 group were lower than those in the PE-1 group,and the differences were statistically significant(P<0.05);the levels of IL-6 and TNF-αin the PE+Tet-2 group were lower than those in the PE-2 group,and the differences were statistically significant(P<0.05).The protein levels of TLR4 and NF-κB in the PE+Tet-1 group were significantly lower than those in the PE-1 group,the differences were statistically significant(P<0.05);the protein levels of TLR4 and NF-κB in the PE+Tet-2 group were significantly lower than those in PE-2 group,the differences were statistically significant(P<0.05).Conclusion T The regulation of TLR4/NF-κB pathway by Tet can reduce blood pressure,decrease 24 h urinary protein,increase placenta and fetal weight,promote fetal development,and inhibit the expression of inflammatory factors in PE rat models.