Effects of electroacupuncture on the oxidative stress in adult rats after cerebral ischemia

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Effects of electroacupuncture on the oxidative stress in adult rats after cerebral ischemia

 

Author: Siu, Ka-wai Flora
Title: Effects of electroacupuncture on the oxidative stress in adult rats after cerebral ischemia
Degree: Ph.D.
Year: 2005
Subject: Hong Kong Polytechnic University -- Dissertations
Electroacupuncture
Oxidative stress
Cerebrovascular disease
Department: Dept. of Rehabilitation Sciences
Pages: xii, 283 leaves : ill. (some col.) ; 30 cm
Language: English
InnoPac Record: http://library.polyu.edu.hk/record=b1809943
URI: http://theses.lib.polyu.edu.hk/handle/200/3007
Abstract: Cerebrovascular disease, especially stroke, is the third leading cause of death in Hong Kong. The conventional treatment and rehabilitation cannot effectively shorten the time for recovery of stroke patients. Another possible treatment, electro-acupuncture (EA), has been used for treating patients with stroke in China. The lack of scientific basis on evaluating its effectiveness restricts its use on patients with stroke in Western countries. This study, therefore, is aimed at investigating its effectiveness on regulating the reactive oxygen species-mediated injury and the apoptotic neuronal damage induced by ischemia-reperfusion in adult rats. Firstly the animal model was induced by the occlusion of middle cerebral artery (MCAO) for 1 hour followed by reperfusion for 1 to 5 days. The severity of model was assessed by the activity and expression of nitric oxide synthase (NOS), activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and the resulting lipid peroxidation (LPX) levels. Results showed that the activity and expression of NOS was increased significantly at day 4 while the activities of SOD and GPx were suppressed, leading to the exacerbation of LPX, which confirmed the successful induction of MCAO in rats. In the second experiment, to investigate the regulation on reactive oxygen species-mediated neurotoxicity, EA stimulation (30 min, 2 Hz, 0.7V) was immediately applied after MCAO. Two pairs of acupuncture points, Fengchi (GB20) and Zusanli (ST36), were individually used for comparison. In comparison to the ischemic condition, inhibited activity and expression of NOS were observed at day 4 after EA stimulation (P<0.05). The concomitant increase of activities of SOD and GPx started as early as 1 day after MCAO and maintained at day 4 (P<0.05). The upregulation of manganese SOD expression was likely due to the increased thioredoxin expression as observed in the following experiment (P<0.05). Owing to the higher removal of reactive oxygen species and diminished formation of peroxynitrite, the LPX levels were greatly attenuated (P<0.05). In the third experiment, the protective effect of EA stimulation against protein oxidation induced by ischemia-reperfusion was monitored by the activity of thioredoxin reductase (TR) and the expression of thioredoxin (Trx). Results showed that EA stimulation could only slightly stimulate the TR activity, but greatly increase the Trx expression (P<0.05), suggesting that the EA stimulation was able to prevent protein oxidation by potentiating the functional level of Trx/TR system. The anti-apoptotic effect of EA stimulation was also investigated in the fourth experiment. Results found that ischemic rats with EA stimulation expressed more anti-apoptotic proteins (TGFb-1, Bcl-2 and pAkt) but less apoptotic proteins (caspase-3 and -9). This down-regulation was likely due to the inhibited BAX translocation and the subsequent release of cytochrome c. Furthermore, the effect of the time to deliver EA stimulation was investigated by the delayed post-ischemia EA stimulation which was applied 1 to 3 days from the onset of MCAO. There was no observable difference between rats with immediate EA stimulation and delayed EA stimulation, suggesting that the effect of EA stimulation was not highly governed by the time. With regard to the clinical consideration, the effect of pre-ischemic EA stimulation was also investigated by giving 3- or 18-times EA stimulation prior to MCAO. The neuroprotective effect was still observed. To sum up, the EA stimulation at GB20 or ST36 could ameliorate the ischemia-reperfusion injury, in which EA stimulation at ST36 produced a better result.

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