Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion.
Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion.
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抑制 CD38/环 ADP-核糖通路可保护大鼠免受罗哌卡因引起的惊厥
DOI：
10.4103/0366-6999.215333
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发表时间：
2017-10-05
影响因子：
6.1
通讯作者：
Guo QL
中科院分区：
文献类型：
--
作者：
Zou Y;He X;Peng QY;Guo QL
背景：CD38/环adp核糖（cADPR）通路在多种中枢神经系统疾病和吗啡耐受中发挥作用，但其在局麻中毒中的作用尚不清楚。本研究的目的是确定CD38/cADPR通路在罗哌卡因诱发惊厥中的作用。方法：40只雄性sd大鼠随机分为5组（每组8只）：假药组、罗哌卡因组、罗哌卡因+8- br - cadpr （5 nmol）组、罗哌卡因+8- br - cadpr （10 nmol）组、罗哌卡因+8- br - cadpr （20 nmol）组，均无大鼠死亡。大鼠在接受罗哌卡因腹腔注射前30分钟脑室内注射生理盐水或8-Br-cADPR。记录脑电图和惊厥行为评分。取各组海马，进行烟酰胺腺嘌呤二核苷酸和cADPR检测、Western blotting分析、丙二醛（MDA）和超氧化物歧化酶（SOD）检测。结果：大鼠腹腔注射罗哌卡因（33.8 mg/kg）引起惊厥。罗哌卡因诱发惊厥后，CD38和cADPR水平显著升高（P分别为0.031和0.020）。脑室内注射8-Br-cADPR（5、10和20 nmol）可显著延长惊厥潜伏期（P分别为0.037、0.034和0.000），缩短惊厥持续时间（P分别为0.005、0.005和0.005），降低惊厥行为评分（P分别为0.015、0.015和0.000）。与罗哌卡因组相比，脑室内注射8-Br-cADPR （10 nmol）增加了b细胞淋巴瘤-2 (Bcl-2)/Bcl-2相关X蛋白比值（P = 0.044），降低了裂解型Caspase 3/Caspase 3比值、诱导型一氧化氮合酶、MDA和SOD水平（P分别为0.014、0.044、0.001和0.010）。结论：CD38/cADPR通路在罗哌卡因引起的惊厥中被激活。抑制这一途径可减轻罗哌卡因引起的惊厥，并保护大脑免受细胞凋亡和氧化应激。
Background: The CD38/cyclic ADP-ribose (cADPR) pathway plays a role in various central nervous system diseases and in morphine tolerance, but its role in local anesthetic intoxication is unknown. The aim of this study was to determine the role of the CD38/cADPR pathway in ropivacaine-induced convulsion. Methods: Forty male Sprague-Dawley rats were randomly divided into five groups (n = 8 per group): sham group, ropivacaine group, ropivacaine+8-Br-cADPR (5 nmol) group, ropivacaine+8-Br-cADPR (10 nmol) group, and ropivacaine+8-Br-cADPR (20 nmol) group (no rats died). Rats were intracerebroventricularly injected with normal saline or 8-Br-cADPR 30 min before receiving an intraperitoneal injection of ropivacaine. Electroencephalography and convulsion behavior scores were recorded. The hippocampus was harvested from each group and subjected to nicotinamide adenine dinucleotide and cADPR assays, Western blotting analysis, and malondialdehyde (MDA) and superoxide dismutase (SOD) assays. Results: Intraperitoneal injection of ropivacaine (33.8 mg/kg) induced convulsions in rats. CD38 and cADPR levels increased significantly following ropivacaine-induced convulsion (P = 0.031 and 0.020, respectively, compared with the sham group). Intraventricular injection of 8-Br-cADPR (5, 10, and 20 nmol) significantly prolonged convulsion latency (P = 0.037, 0.034, and 0.000, respectively), reduced convulsion duration (P = 0.005, 0.005, and 0.005, respectively), and reduced convulsion behavior scores (P = 0.015, 0.015, and 0.000, respectively). Intraventricular injection of 8-Br-cADPR (10 nmol) also increased the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein ratio (P = 0.044) and reduced cleaved Caspase 3/Caspase 3 ratio, inducible nitric oxide synthase, MDA and SOD levels (P = 0.014, 0.044, 0.001, and 0.010, respectively) compared with the ropivacaine group. Conclusions: The CD38/cADPR pathway is activated in ropivacaine-induced convulsion. Inhibiting this pathway alleviates ropivacaine-induced convulsion and protects the brain from apoptosis and oxidative stress.
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影响因子：
5
作者：
Sugimoto, M;Uchida, I;Yoshiya, I
通讯作者：
Yoshiya, I
影响因子：
3.2
作者：
Lin, Pei-Lin;Fan, Shou-Zen;Huang, Chi-Hsiang
通讯作者：
Huang, Chi-Hsiang
影响因子：
3.4
作者：
Pillay, Siveshigan;Liu, Xiping;Hudetz, Anthony G.
通讯作者：
Hudetz, Anthony G.
影响因子：
8.8
作者：
Punke, MA;Friederich, P
通讯作者：
Friederich, P
DOI：
10.1016/0013-4694(72)90177-0
发表时间：
1972-01-01
期刊：
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
影响因子：
--
作者：
RACINE, RJ
通讯作者：
RACINE, RJ