N-乙酰半胱氨酸和曲尼司特對(duì)糖尿病視網(wǎng)膜病變的治療作用與機(jī)制研究
發(fā)布時(shí)間:2018-06-10 00:23
本文選題:N-乙酰半胱氨酸 + 曲尼司特; 參考:《遼寧醫(yī)學(xué)院》2012年碩士論文
【摘要】:目的 觀察N-乙酰半胱氨酸與曲尼司特聯(lián)合使用對(duì)糖尿病大鼠血清氧化應(yīng)激指標(biāo)的影響,并檢測(cè)視網(wǎng)膜TNF-α和NF-κB以及視網(wǎng)膜血管消化鋪片形態(tài),評(píng)估其對(duì)糖尿病視網(wǎng)膜病變的保護(hù)作用。 方法 取健康SD大鼠60只,雌雄各半,隨機(jī)取48只大鼠用鏈脲佐菌素建立糖尿病大鼠模型,隨機(jī)分為糖尿病模型(DM)組,N-乙酰半胱氨酸(NAC)組,曲尼司特(TNL)組,聯(lián)合用藥(COM)組,余12只作為空白對(duì)照(NOR)組。常規(guī)飼養(yǎng)12周觀察視網(wǎng)膜血管消化鋪片形態(tài),并行高倍視野下血管內(nèi)皮細(xì)胞與周細(xì)胞計(jì)數(shù)。測(cè)定大鼠血清GSH與SOD,,免疫組化檢測(cè)視網(wǎng)膜TNF-α,NF-κB的表達(dá)。 結(jié)果 1、一般狀態(tài):飼養(yǎng)期間,NOR組大鼠體重明顯不斷增加,血糖維持正常;其余組體重均增長(zhǎng)緩慢,實(shí)驗(yàn)結(jié)束時(shí)多數(shù)體重較飼養(yǎng)前減輕,血糖與NOR組相比始終在較高水平(P0.01)。 2、免疫組化:NOR組視網(wǎng)膜間少量TNF-α與NF-κB表達(dá),與NOR組相比,各模型組TNF-α與NF-κB均呈較高表達(dá)(P0.01),DM組升高為著;與 DM組相比,用藥組TNF-α與NF-κB表達(dá)均下降(P0.05),以COM組 為著。 3、SOD與GSH含量:與NOR組相比,糖尿病模型及用藥組大鼠GSH與SOD均不同程度降低,其中,DM與TNL組(P0.01)較NAC組和COM組(P0.05)降低顯著,與DM組相比,NAC與COM組GSH和SOD含量較高(P0.05),TNL組與DM組無明顯差異(P0.05)。 4、視網(wǎng)膜血管形態(tài):NOR組大鼠視網(wǎng)膜血管網(wǎng)形態(tài)完整,毛細(xì)血管徑均一;管壁周邊的周細(xì)胞體積稍小,染色深;管腔中央的內(nèi)皮細(xì)胞大,染色淺。DM組血管走行迂曲,欠規(guī)則,直徑不均一,可見無細(xì)胞毛細(xì)血管,周細(xì)胞數(shù)目減少(P0.01)。各治療組均有一定改善,COM組治療作用較明顯 結(jié)論 NAC與TNL聯(lián)合使用對(duì)糖尿病視網(wǎng)膜病變有明顯保護(hù)作用,其作用機(jī)制與拮抗自由基、炎癥反應(yīng)等有關(guān)。
[Abstract]:Objective to observe the effect of combined use of N-acetylcysteine and tranilast on serum oxidative stress in diabetic rats, and to detect retinal TNF- 偽, NF- 魏 B and retinal vascular digestibility paving morphology. Methods Sixty healthy SD rats, half male and female, were randomly selected to establish diabetic rat model with streptozotocin (STZ). The rats were randomly divided into two groups: N- acetylcysteine NACgroup, tranilast TNL group and combined drug control group. The remaining 12 rats were used as blank control group. The morphology of retinal vascular digestion and preparation was observed at 12 weeks after conventional feeding and the vascular endothelial cells and pericytes were counted under high power field of vision. Serum GSH and SOD were measured, and the expression of TNF- 偽 -NF- 魏 B in retina was detected by immunohistochemistry. Results 1. General state: during feeding period, the weight of rats in the nor group increased significantly, the blood glucose maintained normal, and the weight of the other groups increased slowly, and the expression of TNF- 偽 and NF- 魏 B in the retina was detected by immunohistochemistry. At the end of the experiment, most of the body weight was lighter than that before feeding, blood glucose was always at a higher level than nor group (P 0.01). A small amount of TNF- 偽 and NF- 魏 B were expressed in the retina of the small amount of TNF- 偽 and NF- 魏 B in the immunohistochemistry group. Compared with nor group, the expression of TNF- 偽 and NF- 魏 B in each model group was higher than that in the control group (P0.01DM). Compared with the DM group, the expression of TNF- 偽 and NF- 魏 B in the treated group were all decreased (P 0.05), and the contents of SOD and GSH in the com group were decreased. Compared with nor group, the GSH and SOD in the diabetic model group and the drug treated group were decreased in varying degrees, and the levels of GSH and SOD in the DM and TNL groups were significantly lower than those in the NAC group and the com group (P0.05), while the expression of TNF- 偽 and NF- 魏 B in the treated group was significantly lower than that in the control group (P 0.05). Compared with DM group, the content of GSH and SOD in NAC and com group was higher than that in DM group. There was no significant difference between TNL group and DM group. The endothelial cells in the center of the lumen were large, and the blood vessels in the group of light dyed. DM were tortuous, irregular and uneven in diameter. There was no capillary and the number of pericytes decreased (P 0.01). Conclusion NAC combined with TNL has obvious protective effect on diabetic retinopathy, and its mechanism is related to antagonistic free radical and inflammatory reaction.
【學(xué)位授予單位】:遼寧醫(yī)學(xué)院
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2012
【分類號(hào)】:R774.1
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