摘要
目的观察侯氏黑散对脑小血管病(CSVD)模型大鼠内皮屏障的保护作用,探究其分子机制。方法采用自发性高血压大鼠单侧颈总动脉结扎法建立CSVD模型。将大鼠按体质量随机分为假手术组、模型组、侯氏黑散低剂量组、侯氏黑散高剂量组和丁苯酞组。各给药组分别予相应药物灌胃,假手术组和模型组灌胃等量蒸馏水,连续8周。HE染色观察脑血管形态,透射电镜观察血管内皮超微结构,免疫荧光检测白蛋白(Alb)表达,Western blot检测Alb、闭锁小带蛋白-1(ZO-1)、核因子-κB(NF-κB)p65、肌球蛋白轻链激酶(MLCK)和肌球蛋白轻链2(MLC2)蛋白表达。结果与假手术组比较,模型组大鼠血管管腔狭窄,血管周围间隙增大,内皮细胞紧密连接结构破坏,大脑皮层Alb表达显著增强(P<0.01),Alb蛋白表达显著升高(P<0.01),ZO-1蛋白表达显著降低(P<0.05),p-NF-κB p65、MLCK、p-MLC2蛋白表达显著升高(P<0.05,P<0.01);与模型组比较,侯氏黑散低、高剂量组大鼠血管病理损伤和内皮屏障损伤明显减轻,大脑皮层Alb表达显著减弱(P<0.05,P<0.01),侯氏黑散低剂量组Alb、MLCK蛋白表达显著降低(P<0.05,P<0.01),侯氏黑散高剂量组ZO-1蛋白表达显著升高(P<0.05),p-NF-κB p65、MLCK、p-MLC2蛋白表达显著降低(P<0.05,P<0.01)。结论侯氏黑散可减轻CSVD大鼠内皮屏障损伤,其作用机制与调控NF-κB/MLCK/MLC2信号通路有关。
Objective To investigate the protective effects of Hou’s Black Powder on endothelial barrier in a rat model of cerebral small vessel disease(CSVD);To explore its molecular mechanisms.Methods The CSVD model was established in spontaneously hypertensive rats using unilateral common carotid artery occlusion method.Rats were randomly assigned by body mass into sham-operation group,model group,Hou’s Black Powder low-and highdosage groups and butylphthalide group.The treatment groups received the corresponding interventions via oral gavage,while the sham-operation group and model group were administered equal volumes of distilled water.After 8 weeks of continuous treatment,histopathological changes in cerebral vessels was assessed by HE staining,the ultrastructure of vascular endothelium was examined using transmission electron microscopy,albumin(Alb)expression was evaluated by immunofluorescence staining,the expression of Alb,ZO-1,NF-κB p65,myosin light chain kinase(MLCK)and myosin light chain 2(MLC2)were detected by Western blot.Results Compared with the sham-operation group,rats in the model group exhibited marked vascular lumen narrowing,increased perivascular space,disrupted endothelial tight junctions,significantly enhanced Alb expression in cerebral cortex(P<0.01),the expression of Alb protein significantly increased(P<0.01),the expression of ZO-1 protein significantly decreased(P<0.05),and the expressions of p-NF-κB p65,MLCK and p-MLC2 significantly increased(P<0.05,P<0.01).Compared with the model group,vascular pathological damage and endothelial barrier damage of rats in Hou’s Black Powder low-and high-dosage groups were significantly reduced,and the expression of Alb in cerebral cortex was significantly reduced(P<0.05,P<0.01),the expression of Alb and MLCK proteins were significantly decreased in Hou’s Black Powder low-dosage group(P<0.05,P<0.01),while the expression of ZO-1 protein significantly increased in Hou’s Black Powder high-dosage group(P<0.05),the expressions of p-NF-κB p65,MLCK and p-MLC2 proteins were significantly decreased(P<0.05,P<0.01).Conclusion Hou’s Black Powder can alleviate endothelial barrier damage in CSVD rats,and its mechanism of action is related to regulating the NF-κB/MLCK/MLC2 signaling pathway.
作者
王含誉
程宏发
张秋霞
WANG Hanyu;CHENG Hongfa;ZHANG Qiuxia(School of Traditional Chinese Medicine,Capital Medical University,Beijing 100069,China)
出处
《中国中医药信息杂志》
2026年第3期105-111,共7页
Chinese Journal of Information on Traditional Chinese Medicine
基金
国家自然科学基金(82274402)
第五批全国优秀中医临床人才研修项目(2022年)。
