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张亮,唐丽亚,龙轶映,曹佳男,刘梨,赵凌云,瞿启睿,祁芳,艾坤.电针对佐剂性关节炎大鼠膝关节滑膜组织血管内皮生长因子受体2/细胞分裂周期蛋白42信号通路的影响[J].湖南中医药大学学报,2023,43(7):1301-1307[点击复制] |
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电针对佐剂性关节炎大鼠膝关节滑膜组织血管内皮生长因子受体2/细胞分裂周期蛋白42信号通路的影响 |
张亮,唐丽亚,龙轶映,曹佳男,刘梨,赵凌云,瞿启睿,祁芳,艾坤 |
(湖南中医药大学针灸推拿与康复学院, 湖南 长沙 410208;湖南中医药大学附属第一医院, 湖南 长沙 410007) |
摘要: |
目的 观察电针对佐剂性关节炎(adjuvant arthritis,AA)大鼠膝关节滑膜组织内血管内皮生长因子受体2(vascular endothelial growth factor receptor 2,VEGFR2)/细胞分裂周期蛋白42(cell division cycle 42,Cdc42)信号通路的影响,探究电针治疗类风湿关节炎(rheumatoid arthritis,RA)的可能机制。方法 采用随机数字表法将40只SPF级SD雄性大鼠分成空白组、模型组、西药组和电针组,每组10只。模型组、西药组、电针组大鼠采用尾根部皮下注射不完全弗氏佐剂(0.1 mL/只)制成AA大鼠模型。造模后第2天即开始干预,电针组进行电针干预,每次20 min,每天干预1次,共21次,西药组给予甲氨蝶呤灌胃给药,每周1次,共3次。观察各组体质量、关节红肿等一般情况;每3 d测量1次大鼠后双侧足跖容积,干预结束后,通过大鼠一般情况、体质量、足跖容积分析各组大鼠足跖肿胀程度,HE观察各组大鼠滑膜组织的病理形态学变化,免疫组织化学法检测膝关节滑膜组织内VEGFR2、CD34表达变化,Western blot检测大鼠膝关节滑膜组织VEGFR2、Cdc42蛋白表达量。结果 与空白组相比,模型组大鼠第21天足跖容积均明显增大(P<0.01),膝关节滑膜组织出现了显著性病理改变,CD34表达量明显升高(P<0.01),VEGFR2、Cdc42蛋白表达量显著升高(P<0.01)。与模型组相比,西药组、电针组大鼠足趾容积明显减小(P<0.01),膝关节滑膜组织病理改变明显改善,VEGFR2、Cdc42表达量显著下降(P<0.05,P<0.01)。结论 电针改善RA的作用机制可能与降低VEGFR2、Cdc42的表达从而抑制血管新生有关。 |
关键词: 佐剂性关节炎 电针 VEGFR2 Cdc42 血管新生 内皮细胞 伪足 |
DOI:10.3969/j.issn.1674-070X.2023.07.024 |
投稿时间:2022-09-08 |
基金项目:国家自然科学基金项目(82074565);湖南省自然科学基金面上项目(2023JJ30463);长沙市自然科学基金项目(KQ2007072);湖南省研究生科研创新项目(CX20210704);湖南省教育厅科学研究一般项目(21C0254)。 |
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Effects of electroacupuncture on VEGFR2/Cdc42 signaling pathway of knee synovial tissue in rats with adjuvant arthritis |
ZHANG Liang,TANG Liya,LONG Yiying,CAO Jianan,LIU Li,ZHAO Lingyun,QU Qirui,QI Fang,AI Kun |
(School of Acupuncture-moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China) |
Abstract: |
Objective To observe the effects of electroacupuncture on vascular endothelial growth factor receptor 2 (VEGFR2)/cell division cycle 42 (CDC42) signaling pathway of knee synovial tissue in rats with adjuvant arthritis (AA), so as to explore possible mechanism of electroacupuncture in alleviating rheumatoid arthritis (RA). Methods A total of 40 male SPF SD rats were randomly divided into blank group, model group, western medicine group, and electroacupuncture group, with 10 rats in each group. AA rat models were made by subcutaneous injection of incomplete Freund's adjuvant (0.1 mL/rat) at the tail root of rats in model, western medicine, and electroacupuncture groups. On the second day after modeling, the rats in electroacupuncture group were given electroacupuncture for 20 min, once a day, for a total of 21 times, while the rats in western medicine group were given methotrexate intragastrically once a week for 3 times. Then, the general conditions including redness and swelling of joints, body weight, and others in each group were observed. And the volume of bilateral hind paws was measured once every 3 days. After the intervention, the degree of paw swelling of rats in each group was analyzed through the observation of general conditions and the measurement of plantar volume. Meanwhile, the pathomorphological changes of knee synovial tissue was observed by HE staining, the expressions of VEGFR2 and CD34 in synovial tissue of knee joint were determined by immunohistochemistry (IHC), and the protein expressions of VEGFR2 and Cdc42 were examined by Western blot. Results Compared with blank group, the plantar volume of rats in model group increased significantly on the 21st day (P<0.01), the synovial tissue of knee joint showed significant pathological changes, the expression level of CD34, and the protein expression levels of VEGFR2 and Cdc42 were significantly higher (P<0.01). Compared with model group, the plantar volume of rats in western medicine and electroacupuncture groups significantly reduced (P<0.01), the pathological changes of synovial tissue of knee joint were significantly improved, and the expression levels of VEGFR2 and Cdc42 were significantly lower (P<0.05, P<0.01). Conclusion The mechanism of electroacupuncture in improving RA may be related to the inhibition of angiogenesis by reducing the expressions of VEGFR2 and Cdc42. |
Key words: adjuvant arthritis electroacupuncture vascular endothelial growth factor receptor 2 cell division cycle 42 angiogenesis endothelial cells pseudopod |
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