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Part Ⅰ:Protective Effect Of Ruyi Zhenbao Pian On Experimental Cerebral Ischemia In Rats Part Ⅱ:Protective Mechanism Of Antidepressant Duloxetine Hydrochloride OnWater Immersion Restraint Stress-Induced Gastric Ulcer In Rats

Posted on:2014-04-24Degree:MasterType:Thesis
Country:ChinaCandidate:L J GuFull Text:PDF
GTID:2284330470482180Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
The objective was to investigate the protective effect of Ruyi Zhenbao Pian on the motor disturbance after focal cerebral ischemia in rats and the possible protective mechanism of Ruyi Zhenbao Pian on focal cerebral ischemia. Focal cerebral ischemia in male SD rats was induced by permanent middle cerebral artery occlusion (pMCAO).24 h after cerebral ischemia in rats, neurological deficit scores were evaluated, and the content of TNFa in ischemic area was detected by ELISA kit. The behavioral ability was evaluated by the accelerated rotarod test (8,14,21,28,42 d after pMCAO), balance beam test (20 d after pMCAO), footprint test (24 d after pMCAO) and openfield test (28 d after pMCAO). The TTC staining was used to evaluate the infarct volume after 42 d of pMCAO. After 24 h of MCAO, the TNFa and neurological deficit scores were reduced in Ruyi Zhenbao Pian groups. Compared with model group, the neutological scores of Ruyi Zhenbao Pian groups at dose of 0.5,1.0 g·kg-1 were decreased by 14% and 17%, respectively; and the contents of TNFa were decreased by 21% and 55%, respectively. Ruyi Zhenbao Pian at dose of 1.0 g·kg-1 increased remarkably the duration on the rotarod at the 8,14,21,28,42 d after pMCAO, by 50%,33%,47%,46%,159%(P<0.05), respectively; the duration on the balance beam was increased by 71% (P<0.05), and the infarct volume decreased significantly by 41% (P<0.05). but there was no difference on the total distance in the open-field test. In conclusion, Ruyi Zhenbao Pian (i.g.) has potential neuroprotective action against the motor disturbance after the focal cerebral ischemia in rats, and the potential mechanism involved may be related with attenuating the content of TNFa and then resisting the inflammation reaction of the ischemic area.The objective was to investigate the protective effect of Duloxetine Hydrochloride in water immersion restraint stress-induced (WIRS) gastric ulceration, and to explore the antiulcer mechanism of Duloxetine Hydrochloride in the regulation of oxidative stress, inflammation and HPA axis. The pathological section with periodic acid-schiff stain (PAS) of gastric mucosa was used after WIRS 6 h. The contents of reduced glutathione (GSH), MDA and NO, as well as the activities of glutathione peroxidase (GSH-Px), SOD, catalase (CAT) and myeloperoxidase (MPO) in the gastric mucosa were detected after WIRS 6 h. The contents of TNFα, IL-1β, ICAM-1, and NAP-2/CXCL7 in the gastric mucosa were detected after WIRS 6h. The levels of pCREB/CREB, pERK/ERK and pJNK/JNK in the hypothalamus were detected by western bloting after WIRS 6 h. In comparison to sham group, the level of PAS staining and the contents of GSH (P<0.05), SOD (P<0.05), NO (P<0.001), GSH-Px in the gastric mucosa of rats decreased significantly after WIRS 6 h; there was a significant increase in CAT(P<0.001) and MDA(P<0.01) after WIRS 6 h; there showed a significant increase in TNFa(P<0.05), IL-1β(P<0.05), ICAM-1(P<0.01), NAP-2/CXCL7(P<0.05) and MPO (P<0.01) after WIRS 6 h; the phosphorylation of CREB, ERK and JNK was increased in hypothalamic region after WIRS 6 h. Duloxetine hydrochloride reversed the decrease in PAS staining induced by WIRS, and the gastric wall mucus was significantly preserved by the pre-treatment. Duloxetine hydrochloride reversed the oxidative stess reaction, decreased neutrophils infiltration and neutroiphil-endotheliumin adhesion in the gastric mucosa, and inhibited the phosphorylated CREB and ERK except JNK in hypothalamus after WIRS. In conclusion, the pre-treatment of Duloxetine hydrochloride had significantly protective effect on the gastic wall mucus after water-immersion restraint stess-induced gastric ulcer, and the protection may be through inhibiting the oxidative stress reaction and neutrophil-mediated inflammation as well as attenuating the HPA axis activation by the suppression of the CRF mRNA expression.
Keywords/Search Tags:Ruyi Zhenbao Pian, Focal Cerebral Ischemia, MCAO, TNFα, Stress Ulcer, Duloxetine Hydrochloride, Water Immersion Restraint Stress, Inflammation
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