摘要
目的 探讨芹菜素(AP)通过瞬时受体离子通道4(TRPV4)调控蛋白激酶R样内质网激酶(PERK)-增强子结合蛋白同源蛋白(CHOP)内质网应激途径,改善帕金森病(PD)模型大鼠神经功能的机制研究。方法 选取50只大鼠通过6-羟基多巴胺建立PD模型。将大鼠随机分为PD组、AP低剂量(AP-L,20 mg/kg AP)组、AP中剂量(AP-M,40 mg/kg AP)组、AP高剂量(AP-H,80 mg/kg AP)组、TRPV4激活剂(AP-H+4α-PDD,80 mg/kg AP+0.2 mg/kg 4α-PDD)组,每组10只,同时以生理盐水灌胃的10只正常大鼠为对照组。药物治疗结束后,进行大鼠行为学检测,观察其病理学变化、凋亡细胞、超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)、丙二醛(MDA)、酪氨酸羟化酶(TH)表达水平及TRPV4、PERK、CHOP表达情况。结果 与对照组比较,PD组TH阳性表达率、GSH、SOD含量显著降低,旋转圈数、细胞凋亡率、MDA含量、TRPV4、PERK、CHOP表达显著增加(P<0.05);与PD组比较,AP-L组、AP-M组、AP-H组TH阳性表达率、GSH、SOD含量显著增加,治疗后旋转圈数、细胞凋亡率、MDA含量、TRPV4、PERK、CHOP表达显著降低(P<0.05);与AP-H组比较,AP-H+4α-PDD组TH阳性表达率[(15.34±1.54)%vs(30.35±3.04)%]、SOD[(125.84±12.59 vs 185.34±18.55)U/mg]、GSH[(38.46±3.85 vs 75.19±7.52)U/mg]含量显著降低,细胞凋亡率[(26.37±2.64)%vs(11.04±1.11)%]、TRPV4(0.58±0.06 vs 0.23±0.03)、PERK(0.76±0.08 vs 0.38±0.04)、CHOP(0.82±0.09 vs 0.35±0.04)表达显著增加(P<0.05)。结论 AP可以保护PD大鼠神经功能,可能与抑制TRPV4调控PERK-CHOP内质网应激途径有关。
Objective To investigate the mechanism of apigenin(AP) improving the neurological function of rat model of PD through regulating PERK-CHOP endoplasmic reticulum stress pathway via TRPV4.Methods Fifty rats were used to establish PD model by intracerebral injection of 6-hydroxydopamine.Then the rats were randomly divided into PD group, low-(AP-L,20 mg/kg AP),medium-(AP-M,40 mg/kg AP) and high-dose AP(AP-H,80 mg/kg AP) groups, and AP-H+4α-PDD(TRPV4 activator, 80 mg/kg AP+0.2 mg/kg 4α-PDD) group.And another 10 normal rats that were gavaged with normal saline were set as the control group.After the drug treatment, behavioral test was carried out;the brain tissues were collected to observe its pathological changes, apoptotic cells, contents of oxidative stress indicators(including SOD,GSH,MDA) and TH and expression levels of related pathway proteins(TRPV4,PERK and CHOP).Results The positive expression rate of TH and contents of GSH and SOD were significantly lower, while the number of rotations, apoptotic rate, MDA content, and expression levels of TRPV4,PERK and CHOP were significantly higher in the PD group than the control group(P<0.05).And the above indicators were greatly improved in the AP-L group, AP-M group and AP-H group when compared with the PD group(P<0.05).The AP-H+4α-PDD group had obviously lower positive rate of TH [(15.34±1.54)% vs(30.35±3.04)%],SOD content(125.84±12.59 U/mg vs 185.34±18.55 U/mg) and GSH content(38.46±3.85 U/mg vs 75.19±7.52 U/mg),and higher apoptotic rate [(26.37±2.64)% vs(11.04±1.11)%] and enhanced expression levels of TRPV4(0.58±0.06 vs 0.23±0.03),PERK(0.76±0.08 vs 0.38±0.04) and CHOP(0.82±0.09 vs 0.35±0.04) when compared with the AP-H group(P<0.05).Conclusion AP can protect the neurological function of PD rats, which may be related to its inhibition of TRPV4 to regulate the PERK-CHOP endoplasmic reticulum stress pathway.
作者
娄展
彭涛
刘星亮
岳秉宏
李燃
智永怡
Lou Zhan;Peng Tao;Liu Xingliang;Yue Binghong;Li Ran;Zhi Yongyi(Department of Neurology,the First Affiliated Hospital of Hebei North University,Zhangjiakou 050051,Hebei Province,China)
出处
《中华老年心脑血管病杂志》
CAS
北大核心
2023年第2期134-138,共5页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
河北省2020年度医学科学研究课题(20200519)。
关键词
帕金森病
纹状体黑质变性
芹菜素
内质网应激
Parkinson disease
striatonigral degeneration
apigenin
endoplasmic reticulum stress
