基于TLR4/NF-κB通路探讨脑清通汤改善肝热痰瘀型高血压大鼠肾损害作用机制  

Exploration of the Mechanism of Naoqingtong Decoction(脑清通方)on Improving Renal Damage in Hypertensive Rats with Liver Heat and Phlegm Stasis Type Based on TLR4/NF-κB Signal Pathway

作　　者：刘伟[1,2] 宋发萍[1] 张梅奎 李佳晨[1] 王文斌 LIU Wei;SONG Faping;ZHANG Meikui;LI Jiachen;WANG Wenbin(Shaanxi University of Chinese Medicine,Xianyang 712046,Shaanxi,China;Xi'an Shiyou University Hospital,Xi'an 710065,Shaanxi,China;PLA General Hospital,Beijing 100853,China)

机构地区：[1]陕西中医药大学,陕西咸阳712046 [2]西安石油大学医院,陕西西安710065 [3]中国人民解放军总医院,北京100853

出　　处：《辽宁中医药大学学报》2023年第9期38-42,共5页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：陕西省科技厅项目(2020SF-341);陕西省中医学术流派传承工作室项目(陕中医药发[2018]40号)。

摘　　要：目的基于Toll样受体4(TLR4)/核转录因子-κB(NF-κB)通路探讨脑清通汤改善肝热痰瘀型自发性高血压大鼠(spontaneously hypertensive rat,SHR)肾损害的作用机制。方法复制肝热痰瘀型SHR大鼠模型,随机分为空白组(Control),模型组(Model),卡托普利组(Captopri)(10 mg/kg),脑清通汤低(NQTT-L)、中(NQTT-M)、高(NQTT-H)剂量组(7.45、14.90、29.80 g/kg),每组10只。药物组给予上述剂量灌胃,空白组、模型组给予等量生理盐水灌胃,每日1次,持续21 d。用尾动脉搏动法测大鼠灌胃后第7、14、21天的血压。干预结束后采用苏木精-伊红(HE)染色法观测大鼠肾组织变化;实时荧光定量-聚合酶链反应(RT-PCR)技术测定TLR4 mRNA、NF-κBp65 mRNA含量;蛋白印迹(Western blot)法检测TLR4、NF-κBp65蛋白表达情况。结果给药7 d,对比模型组,卡托普利组收缩压差异具有统计学意义(P<0.05);灌胃14 d,与模型组对比,脑清通汤中、高剂量组及卡托普利组大鼠收缩压、舒张压及平均动脉压明显降低(P<0.05或P<0.01);治疗21 d后,与空白组比较,模型组大鼠肾组织结构紊乱,肾小球萎缩,血管硬化扩张,周边大量中性粒细胞及其他炎性细胞浸润,且TLR4mRNA、NF-κBp65 mRNA和TLR4、NF-κBp65蛋白表达明显升高(P<0.05);与模型组对比,脑清通汤各剂量组及卡托普利组肾组织结构紊乱、肾小球萎缩、血管硬化扩张,中性粒细胞及其他炎性细胞浸润情况均不同程度改善,TLR4 mRNA、NF-κBp65 mRNA和TLR4、NF-κBp65蛋白表达明显降低(P<0.05)。结论脑清通汤可能通过抑制TLR4/NF-κB信号通路发挥减轻肝热痰瘀型高血压肾损害的作用。Objective Based on Toll like receptor 4(TLR4)/nuclear transcription factor-κB(NFκB)signal pathway to explore the mechanism of Naoqingtong Decoction(脑清通汤)in improving renal damage in spontaneously hypertensive rats(SHR)of liver heat phlegm stasis type.Methods SHR rats of liver heat and blood stasis type were randomly divided into control group,model group,captopri group(10 mg/kg),Naoqingtong Decoction low-dose((NQTD-L)group,medium-dose(NQTD-M)group,and high-dose(NQTD-H)group(7.45,14.90,29.80 g/kg),with 10 rats in each group.The drug group wasgiven the above dose by gavage,and the blank group and model group were given equal amounts of physiological saline by gavage,once a day for 21 days.The blood pressure of rats was measured by tail artery pulsation method on the 7th,14th and 21st day after gavage.After the intervention,hematoxylin eosin(HE)staining was used to observe the changes of rat kidney tissue;TLR4 mRNA and NF-κB p65 mRNA content were measured by real-time fluorescence quantitative polymerase chain reaction(RT-PCR);TLR4 and NF-κBp65 protein expression were detected by Western blot.Results 7 days after administration,there was a significant difference in systolic blood pressure between the model group and the captopril group(P<0.05).After 14 days of gavage,compared with the model group,the systolic blood pressure,systolic blood pressure and mean arterial pressure of rats in captopril group,NQTD-M group and NQTD-H group were significantly decreased(P<0.05 or P<0.01);After 21 days of treatment,compared with the control group,the renal tissue structure of the model group was disordered,glomerular atrophy,vascular sclerosis and expansion,a large number of neutrophils and other inflammatory cells were infiltrated around,and TLR4 mRNA,NF-κB p65 mRNA and TLR4,NF-κB p65 protein increased significantly(P<0.05);Compared with model group,the renal tissue structure disorder,glomerular atrophy,vascular sclerosis and expansion,neutrophil and other inflammatory cell infiltration were improved in different

关 键 词：TLR4/NF-κB信号通路 脑清通汤 高血压肾损害 炎症 

分 类 号：R259.441[医药卫生—中西医结合] R692[医药卫生—中医内科学]