本文選題：膿毒癥 + 急性腎損傷��； 參考：《大連醫(yī)科大學》2014年碩士論文

【摘要】：目的：探討羅格列酮（Rosiglitazone，ＲＯＳＩ）——PPARγ（Peroxisomeproliferators-activated receptor γ，過氧化物酶增殖激活受體）的配體在膿毒癥急性腎損傷時對大鼠腎臟結構和功能的影響，以及凋亡調控基因Bcl-2在膿毒癥腎臟組織中表達水平的變化，為PPARγ在膿毒癥急性腎損傷中的保護作用提供實驗依據(jù)。 方法：雄性SD大鼠96只隨機分為4組，分別為盲腸結扎穿刺加羅格列酮給藥組（ＣＬＰ+ＲＯＳＩ組）、盲腸結扎穿刺組(ＣＬＰ組)、假手術加羅格列酮給藥組(Sham+ＲＯＳＩ組)、假手術組(Sham組)。采用盲腸結扎穿刺法（Cecal ligation andpuncture，ＣＬＰ）建立膿毒癥模型，ＣＬＰ+ＲＯＳＩ組、ＣＬＰ組術前30分鐘分別腹腔注射羅格列酮（ＲＯＳＩ，10mg/kg）或等體積的藥物溶劑10%二甲基亞砜（DMSO）； Sham+ＲＯＳＩ組、Sham組術前30分鐘分別腹腔注射羅格列酮（ＲＯＳＩ，10mg/kg）或等體積的藥物溶劑10%二甲基亞砜（DMSO）。各組分別在術后0，6，12，24小時各取6只大鼠腹主動脈取血，分離血清檢測肌酐和腫瘤壞死因子α，觀察各組大鼠一般狀態(tài)并應用HE染色檢測腎臟病理組織學變化，檢測腎臟組織的髓過氧化物酶活性（MPO），應用Western blots測定PPARγ及Bcl-2凋亡相關蛋白在腎臟組織中的表達。采用SPSS13.0軟件包對資料進行t檢驗中成組設計兩樣本均數(shù)的檢驗，P0.05為差異具有統(tǒng)計學意義。 結果：ＣＬＰ組肌酐水平隨時間的延長而逐漸升高， ＣＬＰ組與Sham組之間6h肌酐濃度比較無明顯統(tǒng)計學差異（P6=0.812，P0.05），12h、24hＣＬＰ組與Sham之間血清肌酐濃度比較明顯升高（P12=0.047，P24=0.001，P0.05）；ＣＬＰ+ＲＯＳＩ組與Sham+ＲＯＳＩ組之間6h肌酐濃度比較無明顯變化（P6=0.868，P0.05），12h、24hＣＬＰ+ＲＯＳＩ組與Sham+ＲＯＳＩ組之間血清肌酐濃度比較明顯升高（P12=0.033，P24=0.039，P0.05）；0h及6hＣＬＰ+ＲＯＳＩ組與ＣＬＰ組之間血清中肌酐濃度比較無明顯變化（P0=0.418，P6=0.528，P0.05），在12h及24hＣＬＰ+ＲＯＳＩ組與ＣＬＰ組血清肌酐濃度比較，ＣＬＰ+ＲＯＳＩ組血清肌酐的升高較ＣＬＰ組明顯減少（P12=0.04，P24=0.006，P0.05）。6h、12h、24hＣＬＰ組與Sham之間血清TNFα濃度比較有明顯升高（P6=0.00,P12=0.00，P24=0.00，P0.05）；ＣＬＰ+ＲＯＳＩ組與Sham+ＲＯＳＩ組之間6h、12h、24h血清TNFα濃度比較有升高（P6=0.00,P12=0.00，P24=0.00，，P0.05）；6h、12h及24hＣＬＰ+ＲＯＳＩ組與ＣＬＰ組血清TNFα濃度比較，ＣＬＰ+ＲＯＳＩ組血清TNFα濃度升高的水平較ＣＬＰ組明顯降低（P6=0.01，P12=0.02，P24=0.01，P0.05）。0h及6hＣＬＰ+ＲＯＳＩ組與ＣＬＰ組之間腎臟組織髓過氧化物酶活性比較無明顯統(tǒng)計學差異（P0=0.875，P6=0.13，P0.05），在12h及24hＣＬＰ+ＲＯＳＩ組髓過氧化物酶活性升高的水平較ＣＬＰ組有明顯減少（P12=0.01，P24=0.006，P0.05）。ＣＬＰ組髓過氧化物酶活性明顯高于Sham組（P6=0.00,P12=0.00，P24=0.00，P0.05）。ＣＬＰ+ＲＯＳＩ組與Sham+ＲＯＳＩ組之間腎臟組織髓過氧化物酶活性比較有升高（P6=0.00,P12=0.00，P24=0.00，P0.05）。與Sham組和Sham+ＲＯＳＩ組相比，ＣＬＰ+ＲＯＳＩ組、ＣＬＰ組均出現(xiàn)大鼠膿毒癥癥狀，以及器官功能障礙，而ＣＬＰ+ＲＯＳＩ組的大鼠癥狀及器官功能障礙程度較ＣＬＰ組減輕。通過Westernblots測定各組PPAR-γ以及Bcl-2的水平，ＣＬＰ組PPARγ及Bcl-2的表達較ＣＬＰ+ＲＯＳＩ組明顯降低。 結論：羅格列酮作為配體激活PPARγ，從而減輕了膿毒癥時的炎癥反應，減少腎臟細胞凋亡，改善了腎臟功能，減輕腎臟損傷，對大鼠膿毒癥急性腎損傷有保護作用。
[Abstract]:Objective: To investigate the effect of Rosiglitazone (ROSI) - PPAR gamma (Peroxisomeproliferators-activated receptor gamma, peroxidase activation receptor) on the renal structure and function of rats with acute renal injury, and the expression of Bcl-2 in the renal tissue of sepsis. The changes provide an experimental basis for the protection of PPAR gamma in septic acute kidney injury.
Methods: 96 male SD rats were randomly divided into 4 groups, which were cecum ligation and rosiglitazone group (group CLP+ROSI), cecum ligation group (group CLP), sham operation plus rosiglitazone administration group (group Sham+ROSI), sham operation group (group Sham), Cecal ligation ANDPUNCTURE, CL (CL). P) establish a sepsis model, group CLP+ROSI, group CLP, 30 minutes before operation, intraperitoneal injection of rosiglitazone (ROSI, 10mg/kg) or equal volume of drug solvent 10% two methyl sulfoxide (DMSO); group Sham+ROSI, group Sham (ROSI, 10mg/kg) or equal volume of drugs, respectively, 30 minutes before operation. The solvent 10% two methyl sulfoxide (DMSO). Each group took 6 rats' abdominal aorta at 0,6,12,24 hours after the operation to extract the blood from the abdominal aorta. The serum creatinine and tumor necrosis factor alpha were isolated from the serum. The general state of the rats was observed and the renal pathological changes were detected by HE staining, and the myeloperoxidase activity (MPO) in the renal tissue was detected and Western was used to detect the activity of myeloperoxidase (MPO). The expression of PPAR gamma and Bcl-2 apoptosis related protein in renal tissue was measured by blots. The number of two samples in group designed by t test was tested by SPSS13.0 software package, and the difference of P0.05 was statistically significant.
Results: the creatinine level in CLP group increased gradually with time, and there was no significant difference in 6h creatinine concentration between group CLP and Sham group (P6=0.812, P0.05). The serum creatinine concentration between 12h, 24hCLP and Sham was significantly increased (P12=0.047, P24=0.001, P0.05). There was no significant change in the concentration of 6h between I groups (P6=0.868, P0.05), 12h, 24hCLP+ROSI and Sham+ROSI groups increased significantly (P12=0.033, P24=0.039, P0.05), and there was no significant change in serum creatinine concentration between 0h and 6hCLP+ROSI and Sham+ROSI groups. 0.528, P0.05), compared with the serum creatinine concentration in group 12h and 24hCLP+ROSI, the increase of serum creatinine in group CLP+ROSI was significantly lower than that in group CLP (P12=0.04, P24=0.006, P0.05).6h, 12h, and there was a significant increase in the concentration of serum alpha between the 24hCLP group and the CLP group. The concentration of TNF alpha in serum 6h, 12h and 24h between group CLP+ROSI and group Sham+ROSI was higher (P6=0.00, P12=0.00, P24=0.00, P0.05). 1, P12=0.02, P24=0.01, P0.05), there was no significant difference in myeloperoxidase activity between.0h and 6hCLP+ROSI group and CLP group (P0=0.875, P6=0.13, P0.05), and the level of myeloperoxidase activity in 12h and 24hCLP+ROSI group was significantly lower than that in CLP group. .05) myeloperoxidase activity in group.CLP was significantly higher than that in group Sham (P6=0.00, P12=0.00, P24=0.00, P0.05), and the myeloperoxidase activity in renal tissue between.CLP+ROSI and Sham+ROSI groups was increased (P6=0.00, P12=0.00, P24=0.00,). In group CLP, the symptoms of sepsis and organ dysfunction were found in rats, and the degree of symptom and organ dysfunction in the CLP+ROSI group was less than that of the CLP group. The level of PPAR- gamma and Bcl-2 in each group was measured by Westernblots. The expression of PPAR y and Bcl-2 in the CLP group was significantly lower than that in the CLP+ROSI group.
Conclusion: Rosiglitazone activates PPAR gamma as a ligand, thus alleviates the inflammatory response in sepsis, reduces renal cell apoptosis, improves renal function, reduces renal injury, and has a protective effect on acute renal injury in rats with sepsis.

【學位授予單位】：大連醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R459.7

【參考文獻】

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1 陳文秀;陳文激;劉俊;;羅格列酮對急性壞死性胰腺炎及合并肺損傷的防治作用研究[J];臨床合理用藥雜志;2010年15期

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