本文選題：結(jié)核性腦膜炎　切入點(diǎn)：基質(zhì)金屬蛋白酶-9　出處：《南昌大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的： 1、分析基質(zhì)金屬蛋白酶-9(MMP-9)在小鼠結(jié)核性腦膜炎病理過程中的表達(dá)特點(diǎn)及意義。 2、探討單核細(xì)胞-星形膠質(zhì)細(xì)胞網(wǎng)絡(luò)對(duì)MMP-9表達(dá)的作用。 方法： 1、從32只C57BL/6小鼠中隨機(jī)抽取16只,向側(cè)腦室注射10ul含（1.271±0.111）E+6cfu的H37RV菌懸液作為實(shí)驗(yàn)組，另16只用同樣方法注射10ul生理鹽水作為對(duì)照組,30天后處死所有小鼠。 2、分別從兩組中隨機(jī)抽取4只小鼠，取一側(cè)腦組織進(jìn)行結(jié)核菌培養(yǎng)，另一側(cè)進(jìn)行病理HE染色和免疫熒光共聚焦染色。 3、分別從兩組中隨機(jī)抽取4只小鼠，進(jìn)行腦組織明膠酶譜檢測(cè)。 4、分別從兩組中隨機(jī)抽取4只小鼠，進(jìn)行血腦屏障通透性檢測(cè)。 5、分別從兩組中隨機(jī)抽取4只小鼠，進(jìn)行腦組織含水量檢測(cè)。 6、采用兩樣本t檢驗(yàn)比較兩組差異，以P0.05為差異有統(tǒng)計(jì)學(xué)意義。 結(jié)果： 1、實(shí)驗(yàn)組小鼠腦組織勻漿液培養(yǎng)出結(jié)核菌落(4.900±1.407)E+4cfu/ml，病理HE染色表現(xiàn)出蛛網(wǎng)膜下腔、腦室擴(kuò)張，及大量炎癥細(xì)胞浸潤(rùn)等典型腦膜炎病變，，對(duì)照組小鼠腦組織勻漿液均未培養(yǎng)出結(jié)核菌落，病理HE染色未見明顯異常。 2、結(jié)核性腦膜炎小鼠腦組織MMP-9活性明顯增強(qiáng),實(shí)驗(yàn)組明膠酶譜法MMP-9條帶累積光密度值為47821.25±19931.84,對(duì)照組為10081.50±3544.23(t=3.728,P=0.010)，差異有統(tǒng)計(jì)學(xué)意義。 3、結(jié)核性腦膜炎小鼠血腦屏障通透性增加，實(shí)驗(yàn)組腦組織伊文斯蘭含量為11.8239±3.5954ug/g，對(duì)照組為4.6823±3.4009ug/g(t=2.887，P=0.028)，差異有統(tǒng)計(jì)學(xué)意義。 4、結(jié)核性腦膜炎小鼠腦組織含水量增加，實(shí)驗(yàn)組小鼠腦組織含水量比重為0.8492±0.0348，對(duì)照組為0.7752±0.0368(t=2.925，P=0.026)，差異有統(tǒng)計(jì)學(xué)意義。 5、免疫熒光染色顯示實(shí)驗(yàn)組小鼠腦組織中MMP-9、GFAP和OX-42表達(dá)量均明顯增多，且MMP-9與GFAP和OX-42均分別大量重合，表明結(jié)核性腦膜炎小鼠小膠質(zhì)細(xì)胞、星形膠質(zhì)細(xì)胞活化并分泌大量MMP-9。 結(jié)論： 1、MMP-9在結(jié)核性腦膜炎小鼠中活性明顯增強(qiáng)。 2、MMP-9通過分解細(xì)胞外基質(zhì)破壞血腦屏障，促進(jìn)白細(xì)胞、炎性介質(zhì)進(jìn)入 腦組織參與結(jié)核性腦膜炎的病理過程。 3、小膠質(zhì)細(xì)胞-星形膠質(zhì)細(xì)胞網(wǎng)絡(luò)參與調(diào)控MMP-9的分泌。
[Abstract]:Objective:. 1. To analyze the expression and significance of matrix metalloproteinase-9 (MMP-9) in the pathological process of murine tuberculous meningitis. 2. To investigate the effect of monocyte-astrocyte network on MMP-9 expression. Methods:. 1, 16 of 32 C57BL / 6 mice were randomly selected, and 10ul H37RV suspension containing 1.271 鹵0.111Cfu was injected into the lateral ventricle as the experimental group. The other 16 mice were sacrificed after 30 days of injection of 10 ul normal saline as the control group with the same method. 2, 4 mice were randomly selected from the two groups, one side of brain tissue was cultured with tuberculous bacteria, the other side was stained with HE and immunofluorescence confocal staining. 3. Four mice were randomly selected from the two groups to detect the gelatinase spectrum of brain tissue. 4. Four mice were randomly selected from the two groups to detect the blood-brain barrier permeability. 5. Four mice were randomly selected from the two groups to measure the water content of brain tissue. 6, two samples of t test were used to compare the difference between the two groups, with P0.05 as the difference was statistically significant. Results:. 1. The mice in the experimental group were cultured in the homogenate of brain tissue of the experimental group. The mycobacterium tuberculosis was 4.900 鹵1.407E 4cfu-ml. the pathological HE staining showed typical meningitis lesions such as subarachnoid space, ventricular dilatation, and a large number of inflammatory cell infiltration. In the control group, no tuberculous bacteria were found in the homogenate of brain tissue of the control group, and no obvious abnormality was found in the pathological HE staining. (2) the activity of MMP-9 in the brain tissue of mice with tuberculous meningitis was significantly increased. The cumulative optical density of MMP-9 bands in the experimental group was 47821.25 鹵19931.84, and that in the control group was 10081.50 鹵3544.23t0. 728P0.0100.The difference was statistically significant. 3, the permeability of blood-brain barrier increased in mice with tuberculous meningitis. The content of Ivanselam in brain tissue of experimental group was 11.8239 鹵3.5954ugr / g, and that of control group was 4.6823 鹵3.4009ugP / g / g (2.887g / g), the difference was statistically significant. (4) the water content of brain tissue increased in mice with tuberculous meningitis. The proportion of water content in brain tissue of experimental group was 0.8492 鹵0.0348, and that of control group was 0.7752 鹵0.0368. The difference was statistically significant. 5. Immunofluorescence staining showed that the expression of MMP-9 GFAP and OX-42 in the brain tissue of the experimental group was significantly increased, and that the expression of MMP-9, GFAP and OX-42 coincided with each other, indicating that the microglia and astrocytes of the mice with tuberculous meningitis were activated and secreted a large amount of MMP-9. Conclusion:. 1 the activity of MMP-9 was significantly increased in tuberculous meningitis mice. 2MMP-9 destroys the blood-brain barrier by breaking down the extracellular matrix and promotes the entry of leukocytes and inflammatory mediators. Brain tissue is involved in the pathological process of tuberculous meningitis. 3. Microglial-astrocyte network is involved in the regulation of MMP-9 secretion.
【學(xué)位授予單位】：南昌大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R529.3

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本文編號(hào)：1559716