發(fā)布時(shí)間：2018-04-24 06:32

  本文選題：糖尿病性視網(wǎng)膜病變 + 過氧化物酶體增生物激活受體-γ　； 參考：《瀘州醫(yī)學(xué)院》2010年碩士論文

【摘要】：目的：應(yīng)用過氧化物酶體增生物激活受體-y(peroxisome proliferator-activated receptor-gamma, PPAR-y)激動(dòng)劑羅格列酮對(duì)早期糖尿病(diabetes mellitus, DM)大鼠模型進(jìn)行干預(yù),觀察PPAR-y激動(dòng)劑對(duì)DM大鼠視網(wǎng)膜中基質(zhì)金屬蛋白酶-9(matrix metalloproteinases-9,MMP-9)、基質(zhì)金屬蛋白酶-2 (matrix metalloproteinases-2, MMP-2)的表達(dá)及血-視網(wǎng)膜屏障(blood-retina barrier, BRB)通透性的影響,進(jìn)而從分子學(xué)水平上闡明PPAR-y激動(dòng)劑對(duì)早期糖尿病性視網(wǎng)膜病變(diabetic retinopathy, DR)的保護(hù)作用,為預(yù)防及早期治療DR提供一種新思路。方法：選擇114只健康成年雄性Wistar大鼠,隨機(jī)分為正常對(duì)照組(C組,30只),糖尿病組(DM組,42只),DM+羅格列酮組(DM+R組,42只)。予以DM組及DM+R組鏈脲佐菌素(Streptozocin, STZ)按50mg/kg一次性腹腔注射建立DM動(dòng)物模型。將死亡及未成模大鼠剔除出實(shí)驗(yàn)組,按實(shí)驗(yàn)時(shí)間點(diǎn),將以上三組大鼠進(jìn)一步分為C 4w組(10只)、8w組(10只)、12w組(10只),DM 4w組(10只)、8w組(10只)、12w組(10只)及DM+R 4w組(10只)、8w組(10只)、12w組(10只)。自DM模型建立后第三天起,DM+R 4w、8w及12w組每日給予羅格列酮3mg/kg灌胃,每周測(cè)血糖和體重兩次。分別于給藥后4w、8w及12w分別處死各組大鼠,每組各取5只大鼠眼球行BRB通透性測(cè)定；另5只大鼠摘除其左眼球行視網(wǎng)膜消化鋪片觀察視網(wǎng)膜微血管變化情況,計(jì)數(shù)內(nèi)皮細(xì)胞(endothelial cell, E)、周細(xì)胞(perithelial cell, P),計(jì)算E/P值；摘除其右眼球行石蠟包埋,應(yīng)用免疫組化方法檢測(cè)視網(wǎng)膜中MMP-9及MMP-2的表達(dá)情況,并對(duì)實(shí)驗(yàn)結(jié)果進(jìn)行統(tǒng)計(jì)學(xué)分析。結(jié)果：(1)BRB通透性測(cè)定結(jié)果顯示：在各實(shí)驗(yàn)時(shí)間點(diǎn),DM及DM+R組BRB通透性較相應(yīng)C組均增加(P0.01)；DM+R組較相應(yīng)DM組BRB通透性明顯降低(P0.01),且呈時(shí)間依賴性改變；但DM+R組較各相應(yīng)時(shí)間點(diǎn)C組BRB通透性增加(P0.01)。(2)視網(wǎng)膜消化鋪片結(jié)果顯示：DM 4w組與C組及DM+R 4w組比較,所有大鼠視網(wǎng)膜毛細(xì)血管走行、血管壁細(xì)胞數(shù)目及血管形態(tài)均無明顯異常改(P0.05)；DM 8w及12w組與相應(yīng)C 8w及12w組比較,毛細(xì)血管迂曲,管徑粗細(xì)不一,血管壁P數(shù)量明顯減少(P0.01),E數(shù)量增多(P0.01)；在8w及12w時(shí),DM+R組與相應(yīng)的DM組比較,可見血管壁P丟失數(shù)量減少(P0.01),E增生現(xiàn)象減輕(P0.01),且呈時(shí)間依賴性改變；(3)免疫組化檢測(cè)結(jié)果顯示：DM 4w、8w及12w組較相應(yīng)C組MMP-2及MMP-9表達(dá)增多(P0.01)；DM+R各組與相應(yīng)各時(shí)間點(diǎn)的C組比較,MMP-2及MMP-9表達(dá)均增多(P0.01),但與相應(yīng)各時(shí)間點(diǎn)的DM組比較,MMP-2及MMP-9表達(dá)均減少(P0.01)。組內(nèi)比較見C 4w、8w及12w組視網(wǎng)膜中MMP-2陽性表達(dá)細(xì)胞無明顯差異(P0.05)；DM 8w組視網(wǎng)膜中MMP-2及MMP-9陽性表達(dá)細(xì)胞明顯多于DM 4w組(P0.01)；DM 12w組視網(wǎng)膜中MMP-2及MMP-9陽性表達(dá)細(xì)胞明顯多于DM 4w、8w組(P0.01)；DM+R 8w、12w組視網(wǎng)膜中MMP-2及MMP-9陽性表達(dá)細(xì)胞明顯多于DM+R 4w組(P0.01),但DM+R 8w與12w組間比較差異無統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論：(1)采用STZ一次性腹腔注射建立的DM大鼠模型可用于早期DR的相關(guān)研究。(2)MMP-2及MMP-9在早期DR的發(fā)病過程中發(fā)揮著重要作用。(3)PPAR-γ激動(dòng)劑羅格列酮可以抑制早期DM大鼠視網(wǎng)膜中MMP-2及MMP-9的表達(dá),降低BRB通透性,對(duì)早期DM大鼠視網(wǎng)膜具有一定的保護(hù)作用。
[Abstract]:Objective: to use the peroxisome activation receptor -y (peroxisome proliferator-activated receptor-gamma (PPAR-y) agonist, rosiglitazone, to intervene in the rat model of diabetes mellitus (DM), and to observe the matrix metalloproteinase -9 (matrix) in the retinal membrane of DM rats. P-9), the expression of matrix metalloproteinase -2 (matrix metalloproteinases-2, MMP-2) and the influence of the permeability of the blood retinal barrier (blood-retina barrier, BRB), and then elucidate the protective effect of PPAR-y agonists on the early diabetic retinopathy (diabetic retinopathy, DR) from the molecular level, for prevention and early treatment. Method: 114 healthy adult male Wistar rats were selected and randomly divided into normal control group (group C, 30), diabetes group (group DM, 42), DM+ rosiglitazone group (DM+R group, 42 rats). DM group and DM+R group of streptozotocin (Streptozocin, STZ) were injected into DM animal model according to 50mg/kg. Death and unformed models were established. Rats were removed from the experimental group, and the three groups were further divided into C 4W group (10 rats), group 8W (10), group 12W (10), group DM 4W (10), 8W group (10), 12W group (10) and DM+R 4W group (10), 8W group (10), 10 only. Gastric blood glucose and weight were measured two times a week. The rats were killed in each group after 4W, 8W and 12W respectively after administration, respectively, and 5 rats in each group were measured for BRB permeability. The other 5 rats were removed from the left eyeball to observe retinal microvascular changes, counting the endothelial cells (endothelial cell, E), and pericytes (perithelial cell). P), the value of E/P was calculated, paraffin embedded in the right eye was removed and the expression of MMP-9 and MMP-2 in the retina was detected by immunohistochemical method, and the results of the experiment were statistically analyzed. Results: (1) the results of BRB permeability test showed that the BRB permeability of DM and DM +R groups increased (P0.01) in each experiment time point, and the DM+R group was more than that of the DM+R group. The BRB permeability of the corresponding DM group was significantly decreased (P0.01), and the BRB permeability of group DM+R increased (P0.01) compared with the C group at the corresponding time point (P0.01). (2) the results of retinal digestion showed that there was no obvious difference between the DM 4W group and C group and DM+R 4W group, the capillary blood tube of the retina of all rats, the number of vascular wall cells and the morphology of blood vessels were not obvious. Compared with the corresponding C 8W and 12W group, the DM 8W and 12W group were compared with the corresponding C 8W and 12W group. The capillary was circuitous, the diameter of the tube was not one, the number of P in the vessel wall decreased significantly (P0.01), and the number of E increased (P0.01). (3) the results of immunohistochemical detection showed that the expression of MMP-2 and MMP-9 in the group of DM 4W, 8W and 12W increased more than that of the corresponding C group (P0.01), and the MMP-2 and MMP-9 expressions were increased compared with those of the corresponding C groups at the corresponding time points. There was no significant difference in the positive expression of MMP-2 in the membrane (P0.05), and the positive expression of MMP-2 and MMP-9 in the retina of the DM 8W group was more than that of the DM 4W group (P0.01), and the cells in the retina of the retina of the DM 12W group were more than those in the retina, and the positive cells in retina and the retina were more than those in the group of DM 4W. (P0.01), but there is no significant difference between DM+R 8W and 12W group (P0.05). Conclusion: (1) the DM rat model established by one-off intraperitoneal injection of STZ can be used for early DR related studies. (2) MMP-2 and MMP-9 play an important role in the early DR pathogenesis. (3) the PPAR- gamma agonist rosiglitazone can inhibit the early retina of rat retina The expression of MMP-2 and MMP-9 decreased the permeability of BRB and protected the retina of early DM rats.

【學(xué)位授予單位】：瀘州醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類號(hào)】：R774.1

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 哈文靜;嚴(yán)宏;張偉;朱少君;;視網(wǎng)膜血管鋪片技術(shù)的改進(jìn)及在糖尿病視網(wǎng)膜病研究中的運(yùn)用[J];國際眼科雜志;2005年06期

，

本文編號(hào)：1795529