本文選題：化濁解毒活血通絡(luò)法 + 腦缺血再灌注損傷��； 參考：《河北醫(yī)科大學(xué)》2016年碩士論文

【摘要】：目的:本研究在大鼠腦缺血再灌注損傷模型的基礎(chǔ)上,運(yùn)用化濁解毒活血通絡(luò)方進(jìn)行干預(yù),通過對(duì)神經(jīng)功能缺損評(píng)分、腦組織病理形態(tài)改變、用藥后腦梗死體積變化、P-P38MAPK與Caspase-3的觀察,探討該方法是否通過抑制P38MAPK信號(hào)通路來調(diào)控細(xì)胞凋亡,進(jìn)一步闡明化濁解毒活血通絡(luò)法對(duì)受損神經(jīng)元產(chǎn)生保護(hù)作用的內(nèi)在機(jī)制。方法:健康雄性SD大鼠54只,隨機(jī)分為6組:分別是假手術(shù)組、模型組、化濁解毒活血通絡(luò)方低劑量組(以下簡(jiǎn)稱“中藥低劑量組”)、化濁解毒活血通絡(luò)方中劑量組(以下簡(jiǎn)稱“中藥中劑量組”)、化濁解毒活血通絡(luò)方高劑量組(以下簡(jiǎn)稱“中藥高劑量組”)和阿司匹林組。采用改良線栓法制備腦缺血再灌注損傷模型,于造模后第2天給予相應(yīng)藥物治療,假手術(shù)組和模型組給予等量生理鹽水灌胃,中藥各劑量組灌服相應(yīng)濃度的化濁解毒活血通絡(luò)方中藥液,阿司匹林組給予阿司匹林混懸液灌胃。連續(xù)灌胃14d后對(duì)各組大鼠進(jìn)行神經(jīng)功能缺損評(píng)分,處死后斷頭,每組選取3只大鼠取腦,進(jìn)行TTC染色,測(cè)量梗死范圍。其余6只取右側(cè)大腦半球分別進(jìn)行HE染色,光鏡下觀察缺血區(qū)大腦皮質(zhì)組織的形態(tài)變化。PCR法分別檢測(cè)腦皮質(zhì)區(qū)P-P38MAPK和Caspase-3 mRNA的表達(dá)。結(jié)果:1神經(jīng)功能缺損評(píng)分:與假手術(shù)組比較,模型組神經(jīng)功能缺損評(píng)分明顯升高(P0.05);與模型組相比,中藥低劑量組、中藥中劑量組神經(jīng)功能缺損無明顯差異(P0.05),中藥高劑量組、阿司匹林組神經(jīng)功能缺損評(píng)分均降低,差異有統(tǒng)計(jì)學(xué)意義(P0.05);與中藥低劑量組比較,中藥中、高劑量組神經(jīng)功能缺損評(píng)分均下降(P0.05);但中藥高劑量組與阿司匹林組相比,無明顯統(tǒng)計(jì)學(xué)差異(P0.05)。2腦組織病理形態(tài)學(xué)改變:假手術(shù)組大鼠大腦皮層區(qū)腦組織結(jié)構(gòu)正常,細(xì)胞排列整齊緊密,無變性壞死細(xì)胞;模型組大鼠大腦皮層區(qū)可見明顯缺血區(qū),腦組織明顯水腫,神經(jīng)組織排列紊亂,細(xì)胞間隙明顯增大,可見大量的細(xì)胞變性壞死;中藥低劑量組腦組織形態(tài)表現(xiàn)與模型組相似;中藥中劑量組、中藥高劑量組及阿司匹林組缺血區(qū)變性壞死細(xì)胞較模型組減少;中藥高劑量組及阿司匹林組可見少量神經(jīng)壞死細(xì)胞,腦組織形態(tài)無明顯差異。3ttc法檢測(cè)大鼠腦梗死體積:與假手術(shù)組相比,各組均存在較明顯的梗死灶,其中模型組與中藥低劑量組梗死體積無明顯差異(p0.05);中藥中、高劑量組及阿司匹林組梗死體積與模型組相比,均有所減小(p0.05);中藥中、低劑量組腦梗死體積減少均則不及阿司匹林組(p0.05),中藥高劑量組與阿司匹林組相比腦梗死體積無明顯變化(p0.05)。4pcr法檢測(cè)腦組織中caspase-3的表達(dá):與假手術(shù)組相比,模型組caspase-3的表達(dá)水平明顯升高(p0.05);與模型組比較,各用藥組caspase-3的表達(dá)水平均降低(p0.05);與中藥低劑量組比較,中藥中劑量、中藥高劑量組及阿司匹林組caspase-3的表達(dá)降低顯著(p0.05);且中藥中、高劑量組與阿司匹林組比較無明顯統(tǒng)計(jì)學(xué)差異(p0.05)。5pcr法檢測(cè)腦組織中p-p38mapk的表達(dá):與假手術(shù)組比較,模型組p-p38mapk的表達(dá)明顯升高,差異有統(tǒng)計(jì)學(xué)意義(p0.05);與模型組相比,各用藥組p-p38mapk的表達(dá)水平均降低(p0.05);與中藥低劑量組比較,中藥高劑量組及阿司匹林組p-p38mapk的表達(dá)顯著降低(p0.05);而中藥高劑量組的表達(dá)與阿司匹林組相當(dāng),無明顯統(tǒng)計(jì)學(xué)差異(p0.05)。結(jié)論:1化濁解毒活血通絡(luò)方能明顯改善腦缺血再灌注損傷大鼠受損腦組織的病理形態(tài),降低該模型大鼠神經(jīng)功能缺損評(píng)分。2化濁解毒活血通絡(luò)方能夠減小腦缺血再灌注損傷大鼠腦梗死體積,縮小梗死范圍。3化濁解毒活血通絡(luò)方能夠抑制caspase-3的陽(yáng)性表達(dá)及磷酸化p38mapk蛋白的活性,從而減少神經(jīng)細(xì)胞凋亡。4化濁解毒活血通絡(luò)方對(duì)腦缺血再灌注損傷的保護(hù)機(jī)制可能與抑制細(xì)胞凋亡有關(guān),且可能是通過p38mapk信號(hào)通路完成的。
[Abstract]:Objective: on the basis of the model of cerebral ischemia reperfusion injury in rats, the purpose of this study was to intervene with the prescription of chemical detoxification and activating blood dredging collaterals, through the observation of the score of nerve function defect, the pathological changes of brain tissue, the change of cerebral infarction volume after drug use, the observation of P-P38MAPK and Caspase-3, and to explore whether this method can be controlled by inhibiting the P38MAPK signaling pathway. The internal mechanism of cell apoptosis was further clarified. Methods: 54 healthy male SD rats were randomly divided into 6 groups: the sham operation group, the model group, the low-dose group (hereinafter referred to as "the low dose group of Chinese medicine") in the sham operation group (hereinafter referred to as "the low dose group of Chinese medicine"), the huoxioxiu Huoxue Tongluo recipe. The dose group (hereinafter referred to as "the Chinese medicine dose group"), the high dose group (hereinafter referred to as "the high dose group of Chinese medicine") and the aspirin group (hereinafter referred to as "the high dose group of Chinese medicine") and the aspirin group. The model of cerebral ischemia reperfusion injury was prepared by improved thread emboli method. The corresponding drug treatment was given second days after the model building, and the sham operation group and the model group were given the same amount of saline irrigation. The stomach, each dose group of Chinese medicine was given the corresponding concentration of the solution of the decoction of huoxioxiu Huoxue Tongluo, the aspirin group was given the aspirin mixed suspensions. After continuous perfusion of 14d, the nerve function defect was scored in each group. After the death, the brain was taken in each group of 3 rats and the TTC staining was performed to measure the infarct scope. The other 6 only took the right brain. The hemispheres were stained with HE, the morphological changes of cerebral cortex in the ischemic area were observed under light microscope and the expression of P-P38MAPK and Caspase-3 mRNA in the cerebral cortex were detected by.PCR method. Results: 1 the score of nerve function defect was compared with the sham group, the score of neural function defect in the model group was significantly higher (P0.05); compared with the model group, the low dose group of traditional Chinese medicine, There was no significant difference in nerve function defect in the medium dose group (P0.05). The scores of nerve function defect in the high dose group and aspirin group were all lower, the difference was statistically significant (P0.05). Compared with the low dose group of Chinese traditional medicine, the scores of nerve function defect in the high dose group decreased (P0.05), but the high dose group of traditional Chinese medicine was no more than the aspirin group. The pathological changes in the brain tissue of.2 were significantly different (P0.05): the cerebral cortex area of the rats in the sham operation group was normal, the cells arranged neatly and neatly, and the necrotic cells were arranged neatly. The cerebral cortex area of the rats in the model group showed obvious ischemic area, the brain tissue was edema, the nerve tissue was arranged in disorder, and the space between the cells was obviously enlarged, and a large number of them could be seen. The morphology of the brain tissue in the low dose group of Chinese medicine was similar to that in the model group, and the medium dose group, the high dose group and the aspirin group were less than the model group, and the high dose group and the aspirin group showed a small amount of nerve necrotic cells in the high dose group and the aspirin group, and the brain tissue morphology was not significantly different from the.3ttc method. Cerebral infarction volume: compared with the sham group, there were obvious infarcts in all groups, and there was no significant difference in infarct volume between the model group and the low dose group of traditional Chinese medicine (P0.05). The infarct volume in the high dose group and the aspirin group was lower than that in the model group (P0.05), and the decrease of cerebral infarction volume in the low dose group was less than that of the Chinese traditional medicine. Compared with the sham group, the expression level of Caspase-3 in the model group was significantly higher than that in the sham group (P0.05) and the expression level of Caspase-3 in the model group was significantly higher than that in the sham group (P0.05), and the expression level of Caspase-3 in each group was lower (P0.05) than that in the model group (P0.05), compared with the model group (P0.05), compared with the group of the sham operation group (P0.05). Compared with the low dose group, the expression of Caspase-3 in the high dose group and the aspirin group decreased significantly (P0.05), and there was no significant difference between the high dose group and the aspirin group in the traditional Chinese medicine (P0.05).5pcr method to detect the expression of P-P38MAPK in the brain tissue: the expression of P-P38MAPK in the model group was significantly higher than that in the sham operation group. The difference was statistically significant (P0.05). Compared with the model group, the expression level of P-P38MAPK in each group decreased (P0.05). Compared with the low dose group, the expression of P-P38MAPK in the high dose group and the aspirin group decreased significantly (P0.05), while the high dose group was similar to the aspirin group, and there was no significant statistical difference (P0.05). 1 huoxihou Jiedu Huoxue Tongluo recipe can obviously improve the pathological morphology of the damaged brain tissue of the rats with cerebral ischemia reperfusion injury, and reduce the nerve function defect score of the model rats,.2 turbidity, detoxification and activating blood circulation can reduce the volume of cerebral infarction in the rats with cerebellar ischemia reperfusion injury, and reduce the infarct scope to inhibit the CAS of the turbid and activating blood circulation and dredging collaterals. The positive expression of pase-3 and the activity of phosphorylated p38MAPK protein, thus reducing the protective mechanism of neuronal apoptosis,.4, turbid, activating blood circulation and collaterals on cerebral ischemia reperfusion injury, may be related to the inhibition of apoptosis, and may be accomplished through the p38MAPK signaling pathway.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R277.7

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