摘要
目的探讨电针“夹脊穴”调控AMPKα-HDAC5-HIF-1α信号级联对脊髓损伤(SCI)大鼠的治疗机制。方法60只Wister大鼠按体质量随机均分为假手术组、模型组和夹脊电针组,将3组再分为治疗7 d与28 d 2个亚组,每个亚组各10只。除假手术组外,其余大鼠采用重物坠落法(WD)制备SCI模型,造模成功后,夹脊电针组给予电针“夹脊穴”治疗7 d和28 d,采用BBB评分量表和斜坡试验评价大鼠后肢功能、平衡功能的恢复情况;HE染色观察大鼠脊髓组织病理形态学变化,免疫组织化学法检测脊髓组织中Brdu的阳性表达,Western-blot及RT-PCR检测脊髓组织中AMPKα、HDAC5、HIF-1α的蛋白和mRNA表达。结果与假手术组比较,模型组大鼠造模7 d与28 d后BBB评分和斜坡角度明显降低,脊髓组织病理损伤严重,Brdu的阳性细胞数显著增多,HIF-1α的蛋白和mRNA表达明显上调(P<0.01),AMPKα和HDAC5的表达水平未见明显变化(P>0.05);经夹脊电针治疗7 d与28 d后,大鼠BBB评分和斜坡角度显著升高,脊髓组织损伤明显减轻,Brdu的阳性细胞数及HIF-1α的蛋白和mRNA表达较模型组进一步上调,同时明显上调了AMPKα和HDAC5的蛋白及mRNA水平(P<0.01)。结论夹脊电针治疗可能通过促进脊髓组织中AMPKα-HDAC5-HIF-1α信号级联活化,介导损伤组织血管新生,改善SCI脊髓形态,恢复运动功能。
Objective To investigate the therapeutic mechanism of regulating the AMPKα-HDAC5-HIF-1α signaling cascade with electro-acupuncture at Jiaji(EX-B2)in rats with spinal cord injuries(SCI).Methods Sixty Wister rats were randomly divided into a sham operation group,a model group and a Jiaji electro-acupuncture group according to their body mass,and the three groups were further divided into two subgroups for 7 days and 28 days of treatment,with 10 rats in each.Except for the sham operation group,the other rats were used to prepare SCI models by the weight dropping method(WD).After successful modeling,the Jiaji electro-acupuncture group was treated with electro-acupuncture at Jiaji(EX-B2)for 7 and 28 days,respectively,and the recovery of the hind limb function and balance function was evaluated by the BBB scale and ramp test.The pathomorphological changes in the rat spinal cord tissues were observed by HE staining,the positive expression of Brdu in the spinal cord tissues was detected by immunohistochemistry,and the protein and mRNA expressions of AMPKα,HDAC5 and HIF-1α in the spinal cord tissues were detected by Western-blot and RT-PCR.Results Compared with the sham operation group,the BBB scores and slope angle in the model group decreased significantly after 7 and 28 days of modeling,and the pathological injury of the spinal cord was severe,the number of Brdu positive cells increased significantly,and the protein and mRNA expression of HIF-1α was significantly up-regulated(P<0.01),while the expression levels of AMPKα and HDAC5 did not change significantly(P>0.05).After 7 days and 28 days of electro-acupuncture treatment,the BBB scores and slope angle of the rats were significantly increased,the spinal cord tissue injury was significantly reduced,the number of positive cells of Brdu and the protein and mRNA expression of HIF-1αwere further up-regulated compared with the model group,and the expressions of AMPKα and HDAC5 were significantly up-regulated(P<0.01).Conclusion Electro-acupuncture at Jiaji(EX-B2)may promote the activation of AMPKα-HDAC5-HIF-1αsignaling cascade in spinal cord tissues,so as to mediate the angiogenesis of injured tissues,improve the morphology of SCI spinal cord and restore the motor function.
作者
王镌
李玥
蒋伟
王宁
WANG Jun;LI Yue;JIANG Wei;WANG Ning(Department of Traditional Chinese Medicine,the Sixth Affiliated Hospital of Xinjiang Medical University,Urumqi 830092,China;Department of Orthopedics,the Sixth Affiliated Hospital of Xinjiang Medical University,Urumqi 830092,China)
出处
《吉林中医药》
2022年第11期1319-1324,共6页
Jilin Journal of Chinese Medicine
基金
新疆维吾尔自治区自然科学基金资助项目(2021D01C289)。
