β-羟丁酸通过抑制内质网应激发挥对帕金森大鼠的神经保护作用  

The neuroprotective effects of β-hydroxybutyrate on Parkinson’s rats via inhibiting endoplasmic reticulum stress

作　　者：徐巍[1] 王丽霞[1] 刘欣[1] 梁勇[1] 林春花[1] XU Wei;WANG Li-xia;LIU Xin;LIANG Yong;LIN Chun-hua(Department of Neurology,Tieling Central Hospital,Tieling 112001,China)

机构地区：[1]铁岭市中心医院神经内科,辽宁铁岭112001

出　　处：《解剖科学进展》2021年第2期160-163,168,共5页Progress of Anatomical Sciences

摘　　要：目的探究β-羟丁酸(BHBA)对帕金森(PD)模型大鼠的神经保护作用及其机制。方法 SPF级SD大鼠40只,随机分为假手术组(Sham)、模型组(PD)、β-羟丁酸低剂量组(BHBA-L)及β-羟丁酸高剂量组(BHBA-H),每组10只;BHBA-L组及BHBA-H组予以BHBA皮下注射,连续给药24天。观察各组大鼠旋转行为;高效液相色谱(HPLC)检测纹状体内神经递质多巴胺(DA)的含量;免疫组化检测大鼠黑质中酪氨酸羟化酶(TH)及α-突触核蛋白(α-SYN)的表达;Western blot检测大鼠纹状体葡萄糖调节蛋白(GRP78)、C/EBP家族同源蛋白(CHOP)、磷酸化需肌醇酶(p-IRE1)及X盒结合蛋白1(XBP1)的表达。结果BHBA减弱模型大鼠的旋转行为,增加纹状体内DA含量,剂量依赖性增加大鼠黑质中TH的阳性细胞数量并能降低α-SYN的表达水平,降低内质网应激(ERS)指标GRP78、CHOP表达水平及纹状体内p-IRE1及XBP1蛋白的表达水平(P<0.05)。结论 BHBA对帕金森模型大鼠发挥神经保护作用与抑制IRE1-XBP1信号通路,从而抑制ERS有关。Objective To investigate the neuroprotective effect and possible mechanism of β-hydroxybutyrate(BHBA) on Parkinson’s(PD) model rats. Methods Forty SPF grade SD rats were randomly divided into Sham, model group(PD), low-dose beta butyric acid group(BHBA-L) and high-dose beta butyric acid group(BHBA-H), with 10 rats in each group. BHBA was given subcutaneously for 24 days. The rotation behavior of rats was observed. The content of dopamine(DA) in striatum was determined by high performance liquid chromatography(HPLC). The expression of tyrosine hydroxylase(TH) and α-SYN in rat substantia nigra were detected by immunohistochemical staining. The expression of glucose-regulated protein(GRP78), C/EBP family homologous protein(CHOP), phosphorylated inosinolase(p-IRE1) and xbox binding protein 1(XBP1) in rat striatum was detected by Western blot. Results BHBA reduced the rotation behavior of model rats, increased DA content in striatum and TH positive cells in substantia nigra, but decreased α-SYN expression level in dose-dependent manner. BHBA also reduced GRP78 and CHOP expressions of er stress(ERS) and p-IRE1 and XBP1 expressions in striatum(P<0.05). Conclusion The neuroprotective effect of BHBA on Parkinson’s model rats is related to inhibition of p-IRE1-XBP1 signaling pathway and ERS.

关 键 词：羟丁酸 帕金森病 内质网应激 p-IRE1-XBP1信号通路 大鼠 

分 类 号：R593.22[医药卫生—内科学]