本文選題：順鉑 + 急性腎損傷�。� 參考：《廣西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：通過(guò)腹腔注射順鉑建立大鼠急性腎損傷動(dòng)物模型，檢測(cè)血清腫瘤壞死因子-α（TNF-α）、C反應(yīng)蛋白（CRP）、白細(xì)胞介素-6（IL-6）在順鉑致大鼠急性腎損傷中多個(gè)時(shí)間點(diǎn)的變化了解其炎癥反應(yīng)情況，同時(shí)探討還原型谷胱甘肽對(duì)順鉑致大鼠急性腎損傷中上述炎癥因子水平的影響以了解有否腎保護(hù)作用。 方法：54只健康雄性SD大鼠為研究對(duì)象，根據(jù)隨機(jī)數(shù)字法分為生理鹽水對(duì)照組(CN組，n＝6)，順鉑模型組(CP組，n＝24)及還原型谷胱甘肽干預(yù)組(GI組，n＝24)，CP組為腹腔單次注射順鉑10mg/kg，根據(jù)給藥后各時(shí)間點(diǎn)的不同分為CP24h組、CP48h組、CP72h組、CP96h組；GI組為應(yīng)用順鉑前單次腹腔注射還原型谷胱甘肽800mg/kg，然后與CP組一樣使用順鉑，根據(jù)順鉑給藥時(shí)間不同分為GI24h組、GI48h組、GI72h組、GI96h組；每個(gè)時(shí)間點(diǎn)均為6只大鼠。CN組為腹腔注射與CP組等容量的生理鹽水。取各時(shí)間點(diǎn)大鼠乙醚吸入麻醉，打開(kāi)腹腔，門(mén)靜脈取血檢測(cè)血清肌酐(Scr)、TNF-α、CRP、IL-6，立即取出大鼠雙腎，去除被膜，生理鹽水沖洗后，沿冠狀面分為兩部分，用4%多聚甲醛固定過(guò)夜，擬行腎病理切片。 結(jié)果：1.腎功能變化CP組在注射順鉑后24h血Scr較CN組升高不明顯，差別無(wú)統(tǒng)計(jì)學(xué)意義（P＞0.05），48h Scr較CN組明顯升高（P＜0.05），72h Scr較基線升高50%，提示順鉑致大鼠急性腎損傷建模成功；GI組上述時(shí)間點(diǎn)的Scr水平明顯低于CP組（P＜0.05），略高于CN組無(wú)統(tǒng)計(jì)學(xué)差異（P＞0.05）； 2．炎癥因子水平與CN組比較，CP組應(yīng)用順鉑后24h TNF-α即有明顯升高（P＜0.05），隨之呈持續(xù)升高狀態(tài)，至48h達(dá)高峰，72h、96h仍有較高水平；CP組應(yīng)用順鉑后24h血CRP升高明顯（P＜0.05），隨后持續(xù)升高至72h達(dá)高峰，之后下降；CP組應(yīng)用順鉑后72h血IL-6升高明顯（P＜0.05），至96h仍有較高水平；GI組血TNF-α、CRP、IL-6有相似結(jié)果，但與CP組比較水平明顯下降（P＜0.05），與CN組比較上述炎癥因子水平仍有明顯升高。 3．腎臟病理改變NS組大鼠腎組織HE染色可見(jiàn)：腎組織結(jié)構(gòu)清晰未見(jiàn)明顯異常，腎小球、腎小管結(jié)構(gòu)正常，間質(zhì)較少；CP組大鼠腎組織HE染色可見(jiàn)：除有淤積紅細(xì)胞外腎小球未見(jiàn)明顯異常，但腎小管明顯變性，可見(jiàn)腎小管上皮細(xì)胞刷狀緣脫落、胞質(zhì)空泡變性、管腔擴(kuò)張、腎小管堵塞、間質(zhì)炎癥細(xì)胞浸潤(rùn)，，甚至出現(xiàn)聚集凋亡細(xì)胞；且腎小管病變隨時(shí)間逐漸加重。GI組大鼠腎小囊腔隙變窄，腎小管結(jié)構(gòu)完整，細(xì)胞輕度變性、腫脹，少量管腔擴(kuò)張，腔內(nèi)偶見(jiàn)滲出物。 結(jié)論：1.在順鉑致大鼠急性腎損傷中，血清炎癥因子TNF-α、CRP、IL-6升高明顯。 2.還原型谷胱甘肽對(duì)順鉑致大鼠急性腎損傷炎癥反應(yīng)有一定的保護(hù)作用。
[Abstract]:Objective: to establish a rat model of acute renal injury by intraperitoneal injection of cisplatin, and to detect the changes of serum tumor necrosis factor- 偽 (TNF- 偽) C-reactive protein (TNF- 偽) and interleukin-6 (IL-6) in acute renal injury induced by cisplatin in rats. At the same time, the effects of reduced glutathione on the level of inflammatory cytokines in acute renal injury induced by cisplatin in rats were investigated. Methods 54 healthy male Sprague-Dawley rats were studied. According to the random number method, the rats were divided into normal saline control group (CN group), cisplatin model group (CP group) and reduced glutathione intervention group (Glutathione intervention group). The control group was given a single intraperitoneal injection of 10 mg / kg cisplatin. According to the different time points after administration, they were divided into CP24h group (CP48h group) and reduced glutathione intervention group (Glutathione intervention group). Glutathione (800 mg / kg) was injected intraperitoneally before cisplatin was used in GI group, and then cisplatin was used as CP group. According to the time of cisplatin administration, the rats were divided into GI24h group (Gi 48 h) and Gi 72 h group (Gi 96 h group), 6 rats in each group were intraperitoneally injected with normal saline of the same volume as CP group. The rats were anesthetized by ether inhalation at different time points, the abdominal cavity was opened, and the blood samples from portal vein were taken out to detect the serum creatinine, TNF- 偽 and CRP IL-6. The bilateral kidneys of the rats were removed immediately, the membrane was removed. After rinsing with normal saline, the rats were divided into two parts along the coronal surface and fixed with 4% paraformaldehyde for the night. Pathological sections of the kidney were prepared. The result is 1: 1. The changes of renal function in CP group were not significantly higher than those in CN group at 24 h after injection of cisplatin. There was no significant difference in Scr between CN group and CP group (P > 0.05) at 48h. The level of Scr in GI group was significantly lower than that in CP group (P < 0.05), and there was no significant difference between CN group and CN group (P > 0.05). The results showed that the level of Scr in GI group was significantly lower than that in CP group (P < 0.05), and it was slightly higher than that in CN group (P > 0.05). 2. Compared with CN group, the level of inflammatory cytokines in CP group increased significantly 24 hours after cisplatin administration (P < 0.05), and continued to rise, and reached the peak at 48h to 72h / 96h. There was still a higher level of CRP in CP group 24h after cisplatin administration (P < 0.05), and then it continued to rise to the peak at 72 h (P < 0.05). The level of TNF- 偽 in CP group was significantly higher than that in CP group (P < 0.05). After that, the serum IL-6 increased significantly 72 hours after treatment with cisplatin in the CP group (P < 0.05), and there was a similar result at 96 h in the group with high level of TNF- 偽 CRPU IL-6, but the level was significantly lower than that in the CP group (P < 0.05), and the level of the above inflammatory cytokines was still significantly higher than that in the CN group. 3. The pathological changes of kidney in NS group showed that the clear structure of renal tissue was not abnormal, glomeruli and tubule structure were normal. The HE staining in renal tissue of rats with less interstitial protein showed that there was no obvious abnormality in glomeruli except for the accumulation of red blood cells, but the renal tubules were obviously denatured, the brush edge of renal tubule epithelial cells fell off, the cytosolic vacuoles degenerated, the lumen dilated, the renal tubules were blocked, and the renal tubules were blocked. The interstitial inflammatory cells infiltrated and even apoptotic cells appeared, and the renal tubule lesion gradually increased with the time. GI group, the renal tubule structure was intact, the cells were slightly denatured, swelling, a small amount of lumen dilatation. Exudates were occasionally seen in the cavity. Conclusion 1. In the acute renal injury induced by cisplatin, the serum inflammatory factor TNF- 偽 was significantly increased. 2. Reduced glutathione can protect acute renal injury induced by cisplatin in rats.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R730.53;R692.5

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