本文選題：絲膠/藥物 + 糖尿病視網(wǎng)膜病變/生理病理　； 參考：《承德醫(yī)學(xué)院》2017年碩士論文

【摘要】：糖尿病視網(wǎng)膜病變(diabetic retinopathy,DR)是近年來我國最重要的致盲性眼病之一,隨著生活條件的改善和生活方式的改變,DR的發(fā)病率呈逐年上升趨勢。DR的組織病理機(jī)制復(fù)雜,近年的研究認(rèn)為DR是一種輕度的慢性炎癥性疾病,病變早期即出現(xiàn)周細(xì)胞減少和視網(wǎng)膜基底膜增厚等微血管病變,如何早期改善視網(wǎng)膜微血管病變是治療DR的關(guān)鍵。絲膠是蠶繭中的一種天然蛋白質(zhì),由18種氨基酸構(gòu)成。在繅絲和精煉時(shí),約占蠶絲總量25%的絲膠成分被丟棄,造成極大的資源浪費(fèi)。研究發(fā)現(xiàn),絲膠能降低多種炎癥因子的活化能力,具有抗炎作用,且不良反應(yīng)較少。但絲膠能否在DR的疾病過程中發(fā)揮重要的防治作用鮮有研究。本研究采用高脂高糖飲食聯(lián)合鏈脲佐菌素誘導(dǎo)的方法建立2型糖尿病大鼠模型,觀察絲膠對糖尿病模型大鼠視網(wǎng)膜中主要的黏附分子細(xì)胞間黏附分子-1(intercellular adhension molecule-1,ICAM-1)、血管細(xì)胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)及縫隙連接蛋白43(connexin43,Cx43)相對表達(dá)水平的影響,探究絲膠對糖尿病大鼠視網(wǎng)膜微血管損傷的保護(hù)作用,為早期防治DR尋找一條新途徑。目的:觀察絲膠對糖尿病大鼠的視網(wǎng)膜中ICAM-1、VCAM-1和Cx43相對表達(dá)的影響,探討絲膠對糖尿病大鼠視網(wǎng)膜微血管損傷的保護(hù)作用。方法:1將48只SPF級健康雄性SD大鼠,依照計(jì)算機(jī)數(shù)字隨機(jī)分配法,隨機(jī)分為:正常對照組、糖尿病模型組、絲膠治療組和羥苯磺酸鈣陽性藥物對照組,每組大鼠數(shù)量為12只。糖尿病模型組、絲膠治療組和羥苯磺酸鈣陽性藥物對照組大鼠均用高糖高脂飲食聯(lián)合鏈脲佐菌素連續(xù)腹腔注射3d的方法制備2型糖尿病大鼠模型,成模后糖尿病模型組、絲膠治療組和羥苯磺酸鈣陽性藥物對照組大鼠分別用生理鹽水、2.4 g/(kg.d)絲膠溶液和0.2 g/(kg.d)羥苯磺酸鈣溶液灌胃35d。2采用快速血糖儀法檢測各組大鼠的空腹血糖。3蘇木精-伊紅染色觀察各組大鼠視網(wǎng)膜組織的形態(tài)學(xué)變化。4westernblot技術(shù)檢測各組大鼠視網(wǎng)膜組織中icam-1、vcam-1和cx43蛋白的相對表達(dá)量。5逆轉(zhuǎn)錄pcr技術(shù)檢測各組大鼠視網(wǎng)膜組織中icam-1、vcam-1和cx43mrna的相對表達(dá)量。結(jié)果:1各組大鼠的fbg造模前各組大鼠fbg水平無明顯差異,成模時(shí),糖尿病模型組、絲膠治療組和羥苯磺酸鈣陽性藥物對照組大鼠的fbg水平顯著升高(p0.05)。藥物干預(yù)治療后,絲膠治療組和羥苯磺酸鈣陽性藥物對照組與糖尿病模型組相比較,大鼠的fbg水平均顯著降低(p0.05)。2各組大鼠視網(wǎng)膜的組織形態(tài)學(xué)表現(xiàn)正常對照組的大鼠視網(wǎng)膜的組織形態(tài)學(xué)表現(xiàn)正常,糖尿病模型組大鼠視網(wǎng)膜可見內(nèi)界膜腫脹或斷裂,偶見突出于內(nèi)界膜的毛細(xì)血管內(nèi)皮細(xì)胞,rgcs數(shù)量減少,絲膠治療組和羥苯磺酸鈣陽性藥物對照組大鼠視網(wǎng)膜內(nèi)界膜輕度增厚,內(nèi)外核層細(xì)胞排列稍欠規(guī)則。3各組大鼠視網(wǎng)膜組織中icam-1、vcam-1和cx43蛋白的相對表達(dá)量糖尿病模型組大鼠視網(wǎng)膜組織中icam-1和vcam-1蛋白相對表達(dá)量較正常對照組大鼠均顯著升高,而cx43蛋白的相對表達(dá)量顯著下降(均p0.05)。絲膠治療組和羥苯磺酸鈣陽性藥物對照組與糖尿病模型組比較,大鼠視網(wǎng)膜組織中icam-1和vcam-1蛋白的相對表達(dá)量均顯著降低,而cx43蛋白的相對表達(dá)量顯著升高(均p0.05)。4各組大鼠視網(wǎng)膜組織中icam-1、vcam-1和cx43mrna的相對表達(dá)量與正常對照組比較,糖尿病組大鼠視網(wǎng)膜組織中icam-1mrna和vcam-1mrna的相對表達(dá)量均顯著升高,而cx43mrna的相對表達(dá)量顯著下降(均p0.05);絲膠治療組和羥苯磺酸鈣陽性藥物對照組與糖尿病模型組比較,大鼠視網(wǎng)膜組織中icam-1mrna和vcam-1mrna的相對表達(dá)量均顯著下降,而cx43mrna的相對表達(dá)量顯著升高(均P0.05)。結(jié)論:絲膠能夠減輕糖尿病大鼠早期視網(wǎng)膜的微血管病變,從而對DR的發(fā)生和發(fā)展發(fā)揮防護(hù)作用,其機(jī)制可能是下調(diào)視網(wǎng)膜中ICAM-1和VCAM-1的表達(dá)以及上調(diào)Cx43的表達(dá)。
[Abstract]:Diabetic retinopathy (DR) is one of the most important blinding ophthalmopathy in China in recent years. With the improvement of living conditions and the change of life style, the incidence of DR is increasing year by year, and the histopathological mechanism of.DR is complicated. In recent years, the study found that DR is a mild chronic inflammatory disease, and the early pathological changes are Microvascular lesions such as pericytes decrease and retinal basement membrane thickening appear. How to improve retinal microvascular disease early is the key to the treatment of DR. Sericin is a natural protein in silkworm cocoon, consisting of 18 kinds of amino acids. In reeling and refining, the sericin components, which account for about 25% of the total silk, have been discarded, causing great waste of resources. It is found that sericin can reduce the activation of a variety of inflammatory factors, with anti inflammatory effects and less adverse reactions. But it is rarely studied whether sericin can play an important role in the disease process of DR. This study established a model of type 2 diabetic rats with high fat and high sugar diet combined with streptozotocin, and observed sericin on diabetes. The main adhesion molecule intercellular adhesion molecule -1 (intercellular adhension molecule-1, ICAM-1), -1 (vascular cell adhesion molecule-1, VCAM-1) and the relative expression level of connexin 43 in the rat retina of the disease model, to explore the retina microvasculature in diabetic rats The protective effect of injury in order to find a new way for early prevention and control of DR. Objective: To observe the effect of sericin on the relative expression of ICAM-1, VCAM-1 and Cx43 in the retina of diabetic rats, and to explore the protective effect of sericin on retinal microvascular injury in diabetic rats. Methods: 1, 48 SPF grade healthy male SD rats were randomly divided according to the computer digital score. The method was randomly divided into normal control group, diabetic model group, sericin treatment group and calcium hydroxybenzenate positive drug control group. The number of rats in each group was 12. The diabetic model group, the sericin group and the calcium hydroxybenzene sulfonate positive drug control group were prepared with high glucose and high fat diet combined with streptozotocin in continuous intraperitoneal injection of 3D 2. Diabetic rat model, diabetic model group, sericin group and calcium hydroxybenzene sulfonate positive drug control group, rats were treated with saline, 2.4 g/ (kg.d) Sericin Solution and 0.2 g/ (kg.d) hydroxybenzene sulfonate solution to 35d.2 by rapid glucose meter method to detect fasting blood glucose.3 hematoxylin eosin staining in each group. Morphological changes of retinal tissue in rats.4westernblot technique was used to detect the relative expression of ICAM-1, VCAM-1 and Cx43 protein in retina tissue of each group.5 reverse transcriptase PCR technique was used to detect the relative expression of ICAM-1, VCAM-1 and Cx43mRNA in retina tissues of each group. Results: the FBG level in each group of rats in each group of 1 groups was not clear before the model of the rats. The FBG level in the diabetic model group, the sericin therapy group and the calcium hydroxybenzoate positive drug control group increased significantly (P0.05). After the drug intervention, the sericin therapy group and the calcium hydroxybenzoate positive control group were compared with the diabetic model group, and the FBG level of the rats decreased significantly (P0.05) in each group of.2 rats. The histomorphology of the retina of the normal control group was normal. The retina of the diabetic model group could see the swelling or fracture of the inner boundary membrane in the retina of the rats. The number of RGCs in the capillary endothelial cells, which was prominent in the inner boundary membrane, decreased. The retina of the sericin therapy group and the calcium hydroxybenzoate positive drug control group had the inner boundary of the retina. The relative expression of ICAM-1, VCAM-1 and Cx43 protein in retina tissues of.3 rats was slightly thickened, and the relative expression of ICAM-1 and VCAM-1 protein in the retina tissue of the diabetic model group was significantly higher than that of the normal control group, while the relative expression of Cx43 protein decreased significantly (P0.05). Compared with the diabetic model group, the relative expression of ICAM-1 and VCAM-1 protein in the retina tissue of the sericin group and the calcium hydroxybenzene sulfonate positive control group decreased significantly, while the relative expression of Cx43 protein increased significantly (P0.05) in the retina of each group of.4, the relative expression of ICAM-1, VCAM-1 and Cx43mRNA in the retina tissues of each group was normal and normal. Compared with the control group, the relative expression of ICAM-1mRNA and vcam-1mrna in the retina tissues of the diabetic rats increased significantly, while the relative expression of Cx43mRNA decreased significantly (all P0.05). The comparison of the sericin therapy group and the calcium hydroxybenzoate positive control group with the diabetic model group was relative to the ICAM-1mRNA and vcam-1mrna in the retina tissue of the rats. The expression of Cx43mRNA was significantly decreased, while the relative expression of DR was significantly increased (P0.05). Conclusion: sericin can reduce the early retinal microvascular lesions in diabetic rats and protect the occurrence and development of DR. The mechanism may be to downregulate the expression of ICAM-1 and VCAM-1 in the retina and to increase the expression of Cx43.

【學(xué)位授予單位】：承德醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R587.2;R774.1

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