Objective: To observe the effect of electroacupuncture(EA) on glucagon-like peptide-1 receptor (GLP-1R)/ phosphatidylinositol 3-kinase (PI3K)/ protein kinase B(Akt) protein pathway in the substantia nigra of mice with Parkinson's di-sease (PD)，so as to explore its underlying mechanisms in treatment of PD.
Methods: Forty-eight C57BL/6 male mice were randomly divided into normal, model, EA and inhibitor groups, with 12 mice in each group. PD mouse model was established by intragastrical administration of rotenone for 4 weeks. In the EA group, EA was applied at "Fengfu"(GV16), "Taichong"(LR3) and"Zusanli"(ST36) for 30 min, once daily, for 2 weeks. The mice of the inhibitor group received gavage of dipeptidyl peptidase-4 inhibitor ligliptin (10 mg·kg-1·d-1) once a day for 2 weeks. The behavioral scores of mice in each group were observed. The levels of tyrosine hydroxylase (TH) in serum and substantia nigra were detected by ELISA, and the protein relative expression levels of GLP-1R, phosphorylation of PI3K (p-PI3K) and phosphorylation of Akt (p-Akt) in substantia nigra of midbrain of mice were detected by Western blot.
Results: Compared with the normal group, the behavioral scores were significantly increased (P<0.01), TH levels in serum and substantia nigra, protein expression levels of GLP-1R, p-PI3K and p-Akt of the substantia nigra in the model group were significantly decreased (all P<0.01). After intervention and in comparison with the model group, the behavioral scores were significantly decreased (P<0.01), TH levels and the protein expression levels of GLP-1R, p-PI3K and p-Akt in both EA and inhibitor groups were significantly increased (all P<0.01). There were no significant differences in the abovementioned indexes between EA group and inhibitor group (all P>0.05), except for TH levels which were considerably down-regulated in the EA group relative to the inhibitor group (P<0.01, P<0.05).
Conclusion: EA at GV16, LR3 and ST36 may increase the level of TH in serum and substantia nigra by up-regulating the activity of GLP-1R/PI3K/Akt protein pathway, and improve the behavioral performance of PD induced by rotenone.
目的：观察胰高血糖样肽-1受体(GLP-1R)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)蛋白通路在电针治疗帕金森病(PD)小鼠中的作用，探讨电针治疗PD的中脑黑质相关机制。方法：将48只SPF级C57BL/6雄性小鼠随机分为正常组、模型组、电针组、抑制剂组，每组12只。采用鱼藤酮连续灌胃4周制备PD小鼠模型。电针组予电针“风府”“太冲”“足三里”，30 min/次，1次/d，连续干预2周。抑制剂组予二肽基肽酶4抑制剂利格列汀(10 mg·kg-1·d-1)连续灌胃2周。观察各组小鼠行为学评分变化，用酶联免疫吸附测定法检测血清和黑质中酪氨酸羟化酶(TH)水平，用Western blot法检测小鼠中脑黑质中GLP-1R、磷酸化(p)-PI3K、p-Akt蛋白表达水平。结果：与正常组比较，模型组小鼠行为学评分显著升高(P<0.01)，血清和黑质中TH水平均显著降低(P<0.01)，黑质中GLP-1R、p-PI3K、p-Akt蛋白表达水平均显著降低(P<0.01)。治疗后与模型组比较，电针组和抑制剂组小鼠行为学评分均显著下降(P<0.01)，血清和黑质中TH水平均显著升高(P<0.01)，黑质中GLP-1R、p-PI3K、p-Akt蛋白表达水平均显著升高(P<0.01)。与抑制剂组比较，电针组血清和黑质中TH水平降低(P<0.01，P<0.05)。结论：电针“风府”“太冲”“足三里”可能通过上调GLP-1R/PI3K/Akt蛋白通路的活性，提高血清和黑质中的TH水平，从而改善鱼藤酮诱导的PD小鼠行为学表现。.
Keywords: Electroacupuncture; Glucagon-like peptide-1 receptor; Parkinson’s disease; Phosphatidylinositol 3-kinase; Protein kinase B; Tyrosine hydroxylase.