雷公藤红素通过抑制MMP-9/sFlt-1/TNF-α减轻子痫前期模型大鼠症状的作用研究  

Study on Celastrol Alleviating the Symptoms of Preeclampsia Model Rats by Inhibiting MMP-9,sFlt-1 and TNF-α

作　　者：彭敏[1] 胡娅萍[1] 王莹 蒋婷婷[1] 陈朝丽 孙国强[1] Peng Min;Hu Yaping;Wang Ying;Jiang Tingting;Chen Chaoli;Sun Guoqiang(Department of Obstetrics,Hubei Maternal and Child Health Hospital,Wuhan 430070,China)

机构地区：[1]湖北省妇幼保健院产科

出　　处：《中国药师》2020年第1期5-9,共5页China Pharmacist

基　　金：湖北省卫生健康委员会联合基金项目(编号:WJ2019H302)

摘　　要：目的:探讨雷公藤红素通过抑制金属基质酶-9/可溶性FMS样酪氨酸激酶-1/肿瘤坏死因子α(MMP-9/sFlt-1/TNF-α)减轻子痫前期模型大鼠症状的作用机制。方法:72只怀孕未经产的雌性SD大鼠随机分为6组:正常对照组、模型组、硫酸镁组(30mg·kg^-1)、雷公藤红素低、中、高剂量组(10,20,40 mg·kg^-1),每组12只。除正常对照组外,其余各组采用N-硝基-L-精氨酸甲酯盐酸盐诱导子痫前期模型,建模成功后各给药组灌胃给予相应药物,正常对照组和模型组给予等体积生理盐水。于妊娠期(第9天)测定大鼠24 h尿蛋白、血压、尿素氮(BUN),实时荧光逆转录法(RT-PCR)及蛋白质免疫印迹法(West blot)测定胎盘组织MMP-9 mRNA和蛋白水平,酶联免疫吸附法(ELISA)法测定sFlt-1、白细胞介素-4(IL-4)、TNF-α蛋白表达水平。结果:与模型组比较,硫酸镁组、雷公藤红素各剂量组收缩压、舒张压、24 h尿蛋白、BUN水平、MMP-9 mRNA和蛋白、sFlt-1、IL-4、TNF-α蛋白表达水平明显降低(P<0.05),且雷公藤红素各组呈剂量相关性(P<0.05);与硫酸镁组相比,雷公藤红素低、中剂量组以上各指标均明显升高(P<0.05)。结论:雷公藤红素能明显降低子痫前期模型大鼠血压、尿蛋白、BUN水平,缓解子痫前期症状,其机制可能与雷公藤红素通过抑制胎盘组织中MMP-9 mRNA和蛋白表达水平进而降低sFlt-1、IL-4、TNF-α蛋白表达有关。Objective:To investigate celastrol alleviating the symptoms of preeclampsia model rats by inhibiting MMP-9,sFlt-1 and TNF-α.Methods:Totally 72 pregnant female SD rats were randomly divided into 6 groups:the normal control group,the model group,magnesium sulfate group(30 mg·kg^-1),celastrol low,medium and high dose groups(10,20 and 40 mg·kg^-1)with 12 rats in each group.In addition to the normal control group,the other groups used N-nitro-L-arginine methyl ester hydrochloride to induce preeclampsia model.After the successful modeling,each drug-treated group was intragastrically administered with the corresponding drug,and the normal control group and the model group were given an equal volume of physiological saline.During the pregnancy(day9),24 h urine protein,blood pressure and urea nitrogen(BUN)were measured.Real-time fluorescent reverse transcription(RTPCR)and Western blot were used to determine the MMP-9 mRNA and protein levels in placenta,and sFlt-1,interleukin-4(IL-4)and TNF-αprotein expression levels were determined by enzyme-linked immunosorbent assay(ELISA).Results:Compared with those in the model group,systolic blood pressure,diastolic blood pressure,24 h urine protein,BUN level,MMP-9 mRNA and protein,and sFlt-1,IL-4 and TNF-αprotein expression levels significantly decreased(P<0.05),and celastrol groups were in a dose-dependent manner(P<0.05).Compared with those in magnesium sulfate group,all the above indicators in celastrol low and middle dose groups were significantly increased(P<0.05).Conclusion:Celastrol can significantly reduce blood pressure,urinary protein and BUN levels,and alleviate the symptoms of preeclampsia in preeclampsia model rats,and the mechanism may be related to the reduction of sFlt-1,IL-4 and TNF-αprotein expressions by the inhibition of MMP-9 expression and protein level in placenta tissue by celastrol.

关 键 词：雷公藤红素 基质金属蛋白酶-9 子痫前期 可溶性FMS样酪氨酸激酶-1 

分 类 号：R965.1[医药卫生—药理学]