Chen Xiao-Chun, Chen Ying, Zhu Yuan-Gui, Fang Fang, Chen Li-Min
Fujian Institute of Geriatrics, Union Hospital, Fujian Medical University, Fuzhou 350001, China.
Acta Pharmacol Sin. 2002 Sep;23(9):829-34.
To explore the possible mechanism of the ginsenoside Rg1 in protecting substantia nigra neurons from 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced apoptosis in C57BL mice.
C57BL male mice were given with MPTP to prepare Parkinson's disease mouse model. Different doses of Rg1 (2.5, 5.0, and 10.0 mg/kg, respectively) were given 3 d prior to MPTP in the pretreatment groups. Nissl staining, TH immunostaining, and TUNEL labeling were used to observe the damage and apoptosis of nigral neurons. The immunohistochemistry assay was used to detect the protein levels of Bcl-2, Bcl-xl, Bax, inducible nitric oxide synthase (iNOS), neuronal NOS (nNOS), and cleaved caspase-3.
Compared with MPTP model group, pretreatment with Rg1 (5.0 and 10.0 mg/kg) was shown to increase the Nissl staining neurons and TH-positive neurons (P<0.01), and to decrease the TUNEL-positive neurons in the substantia nigra zona compacta (P<0.01). Moreover, Rg1 elevated the levels of cleaved caspase-3, Bax, and iNOS, but reduced the levels of Bcl-2 and Bcl-xl (P<0.01).
Rg1 has protective effect against MPTP-induced apoptosis and this effect may be attributed to enhancing Bcl-2 and Bcl-xl expression, reducing Bax and iNOS expression, and inhibiting activation of caspase-3.
探讨人参皂苷Rg1对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的C57小鼠黑质神经元凋亡的保护作用机制。
给C57雄性小鼠注射MPTP制备帕金森病小鼠模型。预处理组在注射MPTP前3天分别给予不同剂量的Rg1(分别为2.5、5.0和10.0mg/kg)。采用尼氏染色、TH免疫染色和TUNEL标记观察黑质神经元的损伤和凋亡情况。采用免疫组化法检测Bcl-2、Bcl-xl、Bax、诱导型一氧化氮合酶(iNOS)、神经元型一氧化氮合酶(nNOS)和裂解的半胱天冬酶-3的蛋白水平。
与MPTP模型组相比,Rg1(5.0和10.0mg/kg)预处理可增加尼氏染色阳性神经元和TH阳性神经元数量(P<0.01),减少黑质致密部TUNEL阳性神经元数量(P<0.01)。此外,Rg1可提高裂解的半胱天冬酶-3、Bax和iNOS的水平,但降低Bcl-2和Bcl-xl的水平(P<0.01)。
Rg1对MPTP诱导的细胞凋亡具有保护作用,其机制可能与增强Bcl-2和Bcl-xl表达、降低Bax和iNOS表达以及抑制半胱天冬酶-3的激活有关。