本文選題：纈沙坦 + 腹膜透析　； 參考：《青島大學(xué)》2017年碩士論文

【摘要】：目的:觀察纈沙坦對(duì)腹膜纖維化大鼠腹膜結(jié)構(gòu)和超濾功能的影響,以及對(duì)大鼠腹膜組織TGF-β1、p-Smad2/3、Smad7信號(hào)蛋白表達(dá)的影響,進(jìn)一步探討纈沙坦對(duì)腹膜透析大鼠腹膜纖維化的抑制作用及作用機(jī)制,以協(xié)助發(fā)現(xiàn)治療腹膜纖維化作用的新靶點(diǎn)。方法:采用濃度為0.1%的葡萄糖氯己定1.0ml/(100g·d)腹腔注射以建立大鼠腹膜纖維化的模型。實(shí)驗(yàn)共包括三組,30只雄性SD大鼠(清潔級(jí))隨機(jī)分為對(duì)照組、模型組(腹膜纖維化組)、實(shí)驗(yàn)組(模型+纈沙坦組),每組大鼠各10只。三組大鼠均予自由進(jìn)食水,每12小時(shí)晝夜節(jié)律交替照明。適應(yīng)性喂養(yǎng)大鼠1周后開始進(jìn)行實(shí)驗(yàn)。給予對(duì)照組大鼠生理鹽水腹腔注射1.0ml/(100g·d);給予模型組大鼠0.1%葡萄糖氯己定腹腔注射1.0ml/(100g·d);給予實(shí)驗(yàn)組大鼠腹腔注射0.1%葡萄糖氯己定1.0ml/(100g·d)建立大鼠腹膜透析腹膜纖維化模型的同時(shí),將纈沙坦2.0mg/(kg·d)溶于0.5m L 0.9%的生理鹽水中每日予腹腔注射;注射部位均選擇大鼠右下腹部,以上操作共進(jìn)行14天。第14天后,分別測(cè)定三組大鼠的腹膜超濾量,以評(píng)估各組大鼠的腹膜超濾功能。各組大鼠的腹膜超濾量測(cè)量完畢后,處死大鼠,避開腹腔注射進(jìn)針部位留取各組大鼠的壁層及臟層腹膜組織。采取HE染色的方法觀察并對(duì)比三組大鼠壁層腹膜組織的病理學(xué)變改變,采用免疫組化檢測(cè)各組大鼠的壁層腹膜組織轉(zhuǎn)化生長因子β1(TGFβ1)的表達(dá)情況,采用Western-blot檢測(cè)各組大鼠臟層腹膜組織p-Smad2/3及Smad7信號(hào)蛋白的表達(dá)情況。全部實(shí)驗(yàn)數(shù)據(jù)采用SPSS 9.0統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)學(xué)處理,計(jì)量資料用均數(shù)±標(biāo)準(zhǔn)差表示,組間比較采用單因素方差分析。P0.05認(rèn)為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:通過給予大鼠0.1%葡萄糖氯己定腹腔注射,成功復(fù)制了伴有腹膜纖維化的腹膜透析大鼠模型。模型組和實(shí)驗(yàn)組大鼠較對(duì)照組大鼠腹膜超濾量降低,腹膜增厚且伴有腹膜結(jié)構(gòu)紊亂等腹膜纖維化表現(xiàn),且腹膜組織對(duì)TGF-β1、p-Smad2/3、Smad7信號(hào)蛋白的表達(dá)顯著增加。而實(shí)驗(yàn)組與模型組相比較,實(shí)驗(yàn)組大鼠腹膜超濾情況較模型組大鼠明顯改善,腹膜變薄,腹膜結(jié)構(gòu)有一定程度的改善,且實(shí)驗(yàn)組大鼠腹膜對(duì)TGF-β1、p-Smad2/3蛋白的表達(dá)受抑制,作為能夠抑制腹膜TGF-β1表達(dá)的負(fù)反饋因子Smad7蛋白的表達(dá)與能夠上調(diào)TGF-β1的Smad2/3蛋白一樣受到抑制。結(jié)論:(1)纈沙坦能夠一定程度地改善大鼠腹膜結(jié)構(gòu)及超濾功能,抑制大鼠腹膜纖維化進(jìn)程。其抑制作用是過下調(diào)了TGF-β/Smad通路的表達(dá)實(shí)現(xiàn)的。(2)予纈沙坦對(duì)腹膜纖維化的發(fā)展進(jìn)行干預(yù)后,腹膜組織對(duì)TGF-β1及pSmad2/3表達(dá)減少,而對(duì)腹膜纖維化具有抑制作用的信號(hào)蛋白Smad7蛋白的表達(dá)同樣受抑制。
[Abstract]:Aim: to observe the effects of valsartan on peritoneal structure and ultrafiltration function in rats with peritoneal fibrosis, and on the expression of TGF- 尾 1 p-Smad2 / 3 Smad7 signal protein in peritoneal tissue of rats. To further investigate the inhibitory effect and mechanism of valsartan on peritoneal fibrosis in peritoneal dialysis rats in order to find a new target for the treatment of peritoneal fibrosis. Methods: the peritoneal fibrosis model of rats was established by intraperitoneal injection of 0.1% glucose chlorhexidine (1.0ml/(100g d). Three groups of 30 male SD rats (clean grade) were randomly divided into two groups: model group (peritoneal fibrosis group) and experimental group (model valsartan group, 10 rats in each group). All the rats in the three groups were fed freely, and the circadian rhythm was alternately illuminated every 12 hours. The experiment began after 1 week of adaptive feeding. Rats in the control group were given normal saline intraperitoneal injection of 1.0ml/(100g dai; the model group rats were given 0.1% glucoclohexidine intraperitoneal injection of 1.0ml/(100g dai; and the experimental group rats were injected intraperitoneally with 0.1% glucoclohexidine 1.0ml/(100g d) to establish peritoneal fibrosis model of peritoneal dialysis in rats. The valsartan 2.0mg/(kg d was dissolved in 0.5 mL 0.9% normal saline daily and injected intraperitoneally into the right lower abdomen of rats for 14 days. After 14 days, peritoneal ultrafiltration was measured in three groups to evaluate the peritoneal ultrafiltration function of each group. After the peritoneal ultrafiltration measurement was completed, the rats were killed, and the wall and visceral peritoneal tissues of each group were removed from the intraperitoneal injection. The pathological changes of parietal peritoneum in three groups were observed and compared by HE staining. The expression of transforming growth factor 尾 1(TGF 尾 1 (TGF 尾 1) in parietal peritoneum of rats in each group was detected by immunohistochemistry. Western-blot was used to detect the expression of p-Smad2/3 and Smad7 signal proteins in the visceral peritoneum of rats. All the experimental data were statistically processed by SPSS 9.0 statistical software. The measurement data were expressed as mean 鹵standard deviation, and the differences were statistically significant by single factor ANOVA (P0.05). Results: the peritoneal dialysis rat model with peritoneal fibrosis was successfully established by intraperitoneal injection of 0.1% glucose chlorhexidine. Compared with the control group, the peritoneal ultrafiltration (UF) of the model group and the experimental group decreased, the peritoneal thickening accompanied with peritoneal structural disorder and other peritoneal fibrosis manifestations, and the expression of TGF- 尾 1 p-Smad2 / 3 Smad7 signal protein in the peritoneal tissue was significantly increased. Compared with the model group, the peritoneal ultrafiltration in the experimental group was obviously improved, the peritoneum thinned, the peritoneal structure was improved to some extent, and the expression of TGF- 尾 1p-Smad2 / 3 protein was inhibited in the experimental group. The expression of Smad7 protein, a negative feedback factor that can inhibit the expression of TGF- 尾 1 in peritoneum, was inhibited as well as that of Smad2/3 protein which could up-regulate TGF- 尾 1. Conclusion Valsartan can improve the peritoneal structure and ultrafiltration function to some extent and inhibit the process of peritoneal fibrosis in rats. The inhibitory effect of valsartan on the development of peritoneal fibrosis was that the expression of TGF- 尾 1 and pSmad2/3 in peritoneal tissue decreased after the downregulation of the expression of TGF- 尾 / Smad pathway. The expression of signal protein Smad7 was also inhibited in peritoneal fibrosis.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R692.5

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