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及MDA、NO水平均显著升高，Bcl-2蛋白表达量及SOD、GPx水平均显著降低（P＜0.05或P＜0.01）；与甲基苯丙胺组比较，常规剂
量、加倍剂量天麻素组大鼠的刻板行为评分和纹状体的细胞凋亡率、Bax、Cleaved caspase-3、nNOS蛋白表达量及MDA、NO水平
均显著降低，Bcl-2蛋白表达量及SOD、GPx水平均显著升高，且加倍剂量天麻素组大部分上述指标均显著优于常规剂量组（P＜
0.05或P＜0.01）。与NC腺病毒组比较，NC腺病毒+甲基苯丙胺组大鼠纹状体的细胞凋亡率、Bax、Cleaved caspase-3、nNOS蛋白
表达量及 MDA、NO 水平均显著升高，Bcl-2 蛋白表达量及 SOD、GPx 水平均显著降低（P＜0.01）；与 NC 腺病毒+甲基苯丙胺组比
较，NC 腺病毒+天麻素组大鼠纹状体中细胞凋亡率，Bax、Cleaved caspase-3、nNOS 蛋白表达量以及 MDA、NO 水平均显著降低，
Bcl-2蛋白表达量以及SOD、GPx水平均显著升高（P＜0.01）；与NC腺病毒+天麻素组比较，nNOS腺病毒+天麻素组大鼠纹状体中
的细胞凋亡率、Bax、Cleaved caspase-3、nNOS蛋白表达量及MDA、NO水平均显著升高，Bcl-2蛋白表达量及SOD、GPx水平均显著
降低（P＜0.01）。结论：天麻素注射液对甲基苯丙胺诱导的大鼠神经毒性损伤具有明显的保护作用，且这一作用与抑制nNOS介导
的细胞凋亡及氧化应激反应有关。
关键词 甲基苯丙胺；天麻素注射液；神经型一氧化氮合酶；细胞凋亡；氧化应激；机制

Study on the Mechanism of Improvement Effects of Gastrodin Injection on Methamphetamine Induced
Neurotoxic Damage in Rats via nNOS Pathway
XUE Fenglin ，HONG Shijun ，ZENG Xiaofeng ，YANG Genmeng ，ZHOU Yiqing ，LI Lihua （1. Dept. of
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Pathology，the First Affiliated Hospital of Kunming Medical University，Kunming 650032，China；2. College
of Forensic Medicine，Kunming Medical University，Kunming 650500，China）
ABSTRACT OBJECTIVE：To study the mechanism of improvement effects of Gastrodin injection on methamphetamine induced
neurotoxic damage in rats via nNOS pathway. METHODS：SD rats were randomly divided into control group，methamphetamine
group，regular-dose of gastrodin group，double-dose of gastrodin group，negative control（NC）adenovirus group，NC adenovirus+
methamphetamine group，NC adenovirus + gastrodin group and nNOS adenovirus + gastrodin group，with 10 rats in each group.
Control group was given normal saline intraperitoneally，twice a day. Methamphetamine group was given methamphetamine
intraperitoneally（7.5 mg/kg），twice a day. Regular-dose and double-dose of gastrodin groups were respectively given different
doses of Gastrodin injection （10，20 mg/kg） intraperitoneally 30 min earlier，once a day，and then given methamphetamine
intraperitoneally by the same way as methamphetamine group. NC adenovirus group was given NC adenovirus（4.8×10 PFU）3 μL
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once in the striatum and normal saline intraperitoneally，twice a day. NC adenovirus + methamphetamine group was given NC
adenovirus by the same way and methamphetamine（7.5 mg/kg）intraperitoneally，twice a day. NC adenovirus+gastrodin group was
given NC adenovirus+methamphetamine by the same way，meanwhile given Gastrodin injection intraperitoneally（20 mg/kg）30
min before methamphetamine，once a day. nNOS adenovirus+gastrodin group was given nNOS adenovirus and methamphetamine
by the same way，meanwhile given Gastrodin injection intraperitoneally（20 mg/kg）30 min before methamphetamine，once a day.
Each group was given relevant medicine intraperitoneally 1 mL/100 g，for consecutive 3 days. The stereotyped behavior of rats
were observed and scored；the apoptotic rate，the protein expression of apoptotic factors（Bcl-2，Bax，Cleaved caspase-3），the
levels of oxidative stress factors （MDA，SOD，GPx） and NO，the protein expression of nNOS were detected. RESULTS：
Compared with control group，stereotyped behavior score，cell apoptosis rate of striatum，protein expression of Bax，Cleaved
caspase-3 and nNOS，the levels of MDA and NO were increased significantly in methamphetamine group；while the protein
expression of Bcl-2 and the levels of SOD and GPx were decreased significantly （P＜0.05 or P＜0.01）. Compared with
methamphetamine group，stereotyped behavior score，cell apoptosis rate of striatum，protein expression of Bax，Cleaved caspase-3
and nNOS，the levels of MDA and NO were decreased significantly in regular-dose and double-dose of gastrodin groups；while the
protein expression of Bcl-2，the levels of SOD and GPx were increased significantly，and most above indexes in double-dose of
gastradin group were better than regular-dose of gastrodin group（P＜0.05 or P＜0.01）. Compared with NC adenovirus group，cell
apoptosis rate of striatum，protein expression of Bax，Cleaved caspase-3 and nNOS，the levels of MDA and NO were increased
significantly in NC adenovirus+methamphetamine group；while the protein expression of Bcl-2，the levels of SOD and GPx were
decreased significantly（P＜0.01）. Compared with NC adenovirus+methamphetamine group，cell apoptosis rate of striatum，protein
expression of Bax，Cleaved caspase-3 and nNOS，the levels of MDA and NO were decreased significantly in NC adenovirus+
gastrodin group；while the protein expression of Bcl-2，the levels of SOD and GPx were increased significantly （P＜0.01）.
Compared with NC adenovirus+gastrodin group，cell apoptosis rate of striatum，protein expression of Bax，Cleaved caspase-3 and
nNOS，the levels of MDA and NO were increased significantly in nNOS adenovirus+gastrodin group；while the protein expression
of Bcl-2，the levels of SOD and GPx were decreased significantly（P＜0.01）. CONCLUSIONS：Gastrodin injection can protect
rats against neurotoxic damage induced by methamphetamine，and the effect is related to the inhibition of nNOS-mediated apoptosis
and oxidative stress.
KEYWORDS Methamphetamine；Gastrodin injection；nNOS；Cell apoptosis；Oxidative stress；Mechanism

·1172 · China Pharmacy 2020 Vol. 31 No. 10 中国药房 2020年第31卷第10期