摘要
目的探讨川陈皮素调节Ras同源基因家族成员A(RhoA)/Rho相关的卷曲螺旋激酶(ROCK)信号通路对妊娠高血压(PIH)大鼠内皮功能障碍的影响。方法取SD大鼠雌雄合笼制备孕鼠,通过灌胃N-硝基-左旋精氨酸甲酯(L-NAME)构建PIH大鼠模型,随机分为模型组、川陈皮素低剂量(3.6 mg/kg)组、川陈皮素高剂量(7.2 mg/kg)组、川陈皮素高剂量(7.2 mg/kg)+溶血磷脂酸(LPA)(RhoA/ROCK信号激活剂,1 mg/kg)组,每组均10只孕鼠,另取10只孕鼠灌胃等剂量生理盐水设为对照组,采用川陈皮素和LPA分组处理后,测量各组大鼠血压;检测各组大鼠24 h尿蛋白含量并以H-E染色检测其肾组织与胎盘组织病理形态;以酶联免疫吸附测定(ELASA)法检测各组大鼠血清内皮功能生物标志因子内皮素1(ET-1)、血栓素B2(TXB2)、一氧化氮(NO)与炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL-17水平;以免疫印迹法检测各组大鼠胎盘组织RhoA/ROCK通路相关蛋白表达。结果与对照组比较,模型组大鼠肾组织与胎盘组织形态发生严重病理损伤,收缩压、舒张压、平均动脉压、24h尿蛋白含量、血清ET-1、TXB2、TNF-α、IL-6与IL-17水平、胎盘组织RhoA、ROCK1与ROCK2蛋白表达升高(P<0.05),血清NO水平降低(P<0.05);与模型组比较,川陈皮素低剂量组、川陈皮素高剂量组大鼠肾组织与胎盘组织形态病理损伤均减轻,收缩压、舒张压、平均动脉压、24 h尿蛋白含量、血清ET-1、TXB2、TNF-α、IL-6与IL-17水平、胎盘组织RhoA、ROCK1与ROCK2蛋白表达均降低(P<0.05),血清NO水平均升高(P<0.05),且高剂量川陈皮素作用更强;LPA可减弱川陈皮素对PIH模型大鼠的作用。结论川陈皮素通过抑制RhoA/ROCK信号激活而抑制PIH大鼠炎症,从而改善大鼠内皮功能障碍,并减轻其肾脏及胎盘组织损伤,最终缓解大鼠高血压症状。
Objective To investigate the effect of nobiletin on endothelial dysfunction in pregnancy-induced hypertension(PIH)rats by regulating the Ras homolog gene family,member A(RhoA)/Rho associated coiled coil-forming kinase(ROCK)signaling pathway.Methods Pregnant SD rats were prepared from male and female caged rats.The PIH rat model was established by gavage of N-nitro-L-arginine methylester(L-NAME).They were randomly grouped into model group,low dose(3.6 mg/kg)nobiletin group,high dose(7.2 mg/kg)nobiletin group,high dose(7.2 mg/kg)nobiletin+lysophosphatidic acid(LPA)(RhoA/ROCK signal activator,1 mg/kg)group,with 10 pregnant rats in each group,another 10 pregnant mice were given an equal dose of physiological saline by gavage as the control group.After treating with nobiletin and LPA,blood pressure of rats in each group was measured.The 24-hour urine protein content of rats in each group was detected,and H-E staining was applied to detect the pathological morphology of their renal and placental tissues.Enzyme linked immunosorbent assay(ELASA)was applied to detect the levels of serum endothelin 1(ET-1),thromboxane B2(TXB2),nitric oxide(NO),tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-17,the biomarkers of endothelial function in rats of each group.Immunoblotting was applied to detect the expression of RhoA/ROCK pathway related proteins in placental tissue of rats in each group.Results Compared with the control group,the renal and placental morphogenesis of the model group rats suffered severe pathological damage,the systolic blood pressure,diastolic blood pressure,mean arterial pressure,24-hour urine protein content,the levels of serum ET-1,TXB2,TNF-α,IL-6 and IL-17,and the expression of RhoA,ROCK1 and ROCK2 proteins in placental tissue increased(P<0.05),the level of serum NO decreased(P<0.05).Compared with the model group,the morphological and pathological damages of renal tissue and placental tissue of rats in the low dose nobiletin group and the high dose nobiletin group were alleviated,the systolic blo
作者
谷孝月
刘志明
赵会新
蒋天从
GU Xiaoyue;LIU Zhiming;ZHAO Huixin;JIANG Tiancong(Prenatal Diagnosis Center,Tangshan Maternal and Child Health Hospital,Tangshan,Hebei 063000,China;Department of Pharmacy,Affiliated Hospital of North China University of Science and Technology,Tangshan,Hebei 063000,China)
出处
《中国优生与遗传杂志》
2024年第1期41-47,共7页
Chinese Journal of Birth Health & Heredity
基金
2022年河北省医学科学研究课题计划项目(20221770)。
