【摘要】：目的:探討胃旁路手術對高尿酸血癥大鼠血尿酸、血脂、血糖等代謝指標的影響,分析可能機制。方法:8周齡的雄性Wistar大鼠40只隨機分組為空白對照組(C,n=10)和模型組(M,n=30)。模型組給予高嘌呤飲食加腺嘌呤混懸液灌胃處理建立高尿酸血癥模型,空白對照組正常飲食。建模成功后將模型組隨機分為高尿酸血癥組(H,n=10)、假手術組(Sham,n=10)和胃旁路手術組(RYGB,n=10),并對其進行相應處理,手術后大鼠普通飲食。分別于手術前,術后2周、4周、6周和8周大鼠靜脈取血,檢測其血尿酸、血糖、甘油三酯、膽固醇、肌酐、尿素氮和胰島素水平的變化,并計算胰島素抵抗指數(shù)HOMA-IR值比較胰島素抵抗的差異。手術前留取糞便標本,術后8周后處死大鼠,留取糞便、相應組織器官和血液標本,留待菌群、代謝組學和相關組織病理的檢測,進一步探究可能的機制。結果:手術前,四組大鼠的體重無顯著統(tǒng)計學差異(分別為327.6±16.37 vs 313.8±17.32 vs 316.5±16.96 vs 319.5±19.98,p均0.05)。手術8周后,RYGB組體重顯著下降,明顯低于其他三組(分別為248.6±15.08 vs 416.2±21.08,248.6±15.08 vs411.7±22.82和248.6±15.08 vs 398.3±18.81,p均0.05)。建模4周后,模型組大鼠與空白對照組相比,血尿酸水平明顯升高(235.33±17.85 vs 108.37±13.64,p0.05),表示成功建立高尿酸血癥大鼠模型。手術后8周,3組模型組大鼠的血尿酸水平均有不同程度的下降,然而RYGB組血尿酸水平下降更明顯,接近于對照組的正常水平(114.03±9.21 vs 122.21±10.33,p0.05),而高尿酸組和假手術組仍高于空白對照組(分別為184.67±11.53 vs 114.03±9.21;和189.32±15.81 vs 114.03±9.21,p均005),而伴隨血尿酸的下降,肌酐和尿素氮也出現(xiàn)降低,其中胃旁路組與空白對照組無明顯差異(分別為20.82±4.67 vs 19.20±3.12和8.02±1.66 vs 7.17±1.64,p均大于0.05)。而對于其他的代謝指標,血糖在手術前3個實驗組與空白對照組有明顯的差異(分別為6.61±0.39,6.51±0.47,6.59±0.57 vs 4.26±0.58,p均0.05),而在術后8周,胃旁路手術組明顯下降,與空白對照組無差異(4.67±0.43 vs 4.01±0.54,p0.05),其余高尿酸組和假手術組無明顯變化,與空白對照組有明顯差異(分別為6.69±0.48,6.86±0.52 vs 4.01±0.54,p均0.05);血甘油三酯在術前,3個實驗組與空白對照組有明顯差異(分別為1.14±0.24,1.20±0.22,1.18±0.18 vs 0.58±0.24,p均0.05),手術后,3個實驗組較術前均有不用程度的下降,3個組與空白對照組無差異(分別為0.86±0.22,0.89±0.18,0.66±0.21 vs 0.61±0.19,p均0.05),而胃旁路組較其余兩個實驗組下降趨勢更為明顯,下降幅度更大;血膽固醇水平3組手術后均有下降,其中胃旁路組下降顯著,與空白對照組無顯著差異(1.51±0.28 vs1.43±0.27,p0.05),其余兩組與空白對照組相比仍有差異(分別為2.16±0.29,2.19±0.30 vs 1.43±0.27,p均0.05)。通過計算胰島素抵抗指數(shù)HOMA-IR值我們發(fā)現(xiàn),術前3個實驗組與空白對照組出現(xiàn)顯著性差異(分別為3.92±0.52,3.86±0.49,3.82±0.51 vs 2.24±0.38,p均0.05),術后8周,胃旁路組胰島素抵抗明顯緩解,與空白對照組無明顯差異(2.19±0.42 vs 2.08±0.41,p0.05),而高尿酸組和假手術組仍然高于空白對照組(分別為3.45±0.57,3.51±0.52 vs 2.08±0.41,p均0.05).結論:胃旁路手術能夠明顯改善高尿酸血癥大鼠的血尿酸水平,同時糾正高尿酸血癥血糖、血脂的代謝紊亂和腎功能的影響,緩解胰島素抵抗。其機制可能與胃旁路手術后腸道激素的分泌改變和菌群及產(chǎn)物的變化引起代謝和炎癥通路的緩解有關。
[Abstract]:Objective: To investigate the effect of gastric bypass surgery on the metabolic indexes of uric acid, blood lipid and blood glucose in hyperuricemia rats, and to analyze the possible mechanism. Methods: 40 male Wistar rats of 8 weeks old were randomly divided into blank control group (C, n=10) and model group (M, n=30). The model group was given high urine with hyperpurine diet plus adenine suspension to establish high uric acid blood. After the modeling success, the model group was randomly divided into the hyperuricemia group (H, n=10), the sham operation group (Sham, n=10) and the gastric bypass surgery group (RYGB, n=10), and the rats were treated accordingly. After the operation, the rats were treated with the normal diet. The blood uric acid was measured at 2 weeks, 4 weeks, 6 weeks and 8 weeks after the operation. The changes in blood sugar, triglyceride, cholesterol, creatinine, urea nitrogen and insulin levels and the difference between the HOMA-IR value of the insulin resistance index and the difference between the insulin resistance were calculated. The rats were left out before the operation and 8 weeks after the operation, the rats were killed, the excrement was left, the corresponding tissues and blood samples were left, the bacteria group, the metabolomics and the related histopathological examination were kept. Test, further explore the possible mechanism. Results: before operation, there was no significant difference in weight between the four groups (327.6 + 16.37 vs, 313.8 + 17.32 vs, 316.5 + 16.96 vs 319.5 + 19.98, and 0.05). After 8 weeks of operation, the body weight of RYGB group was significantly lower than that of other three groups (248.6 + 16.37 + vs + 21.08248.6 + vs411, respectively. .7 + 22.82 and 248.6 + 15.08 vs 398.3 + 18.81, P 0.05). After modeling for 4 weeks, the blood uric acid level in the model group was significantly higher than that in the blank control group (235.33 + 17.85 vs 108.37 +, P0.05), indicating that the hyperuricemia rat model was successfully established. The decrease of serum uric acid level in RYGB group was more obvious, which was close to the normal level of the control group (114.03 + 9.21 vs 122.21 + 10.33, P0.05), while the high uric acid group and sham group were still higher than the blank control group (184.67 + 11.53 vs 114.03 + 9.21 respectively, and 189.32 + 15.81 vs 114.03 + 9.21, P 005), with the decrease of serum uric acid, creatinine and urea nitrogen There was no significant difference between the gastric bypass group and the blank control group (20.82 + 4.67 vs 19.20 + 3.12, 8.02 + 1.66 vs 7.17 + 1.64, P greater than 0.05). For other metabolic indicators, there was a significant difference between the blood sugar and the blank control group before the operation (6.61 + 0.39,6.51 + 0.47,6.59 + 0.57 vs 4.26 +% respectively, respectively). P was 0.05), but in the 8 week after the operation, the gastric bypass surgery group decreased significantly, and no difference was found in the control group (4.67 + 0.43 vs 4.01 + 0.54, P0.05). The other high uric acid group and sham group had no obvious changes, and there was a significant difference between the control group and the blank control group (6.69 + 0.48,6.86 + 0.52 vs 4.01 + 0.54, P mean 0.05). There were significant differences in the blank control group (1.14 + 0.24,1.20 + 0.22,1.18 + 0.18 vs 0.58 + 0.24, P 0.05). After the operation, the 3 experimental groups were less than before the operation, and there was no difference between the 3 groups and the blank control group (0.86 + 0.22,0.89 + 0.18,0.66 + 0.21 vs 0.61 + 0.19, P 0.05), while the gastric bypass group was more than the rest of the experimental group. The decline trend was more obvious and the decrease was greater; the blood cholesterol level 3 groups decreased after operation, and the gastric bypass group decreased significantly, and there was no significant difference from the blank control group (1.51 + 0.28 vs1.43 + 0.27, P0.05). The other two groups were still different from the blank control group (2.16 + 0.29,2.19 + 0.30 vs 1.43 + 0.27, P 0.05). The HOMA-IR value of insulin resistance index was found to show significant difference between the 3 experimental groups and the blank control group (3.92 + 0.52,3.86 + 0.49,3.82 + 0.51 vs 2.24 + 0.38, P 0.05). The insulin resistance in the gastric bypass group was significantly relieved at the end of the operation, and there was no significant difference between the control group and the blank control group (2.19 + 0.42 vs 2.08 +, P0.05), and high urine. The acid group and the sham operation group were still higher than the blank control group (3.45 + 0.57,3.51 + 0.52 vs 2.08 + 0.41, P 0.05 respectively). Conclusion: gastric bypass surgery can obviously improve the level of uric acid in hyperuricemia rats, and correct the hyperuricemia, the metabolic disorder of blood lipid and the effect of renal function, and alleviate the insulin resistance. It is associated with changes in gut hormone secretion and changes in flora and products after gastric bypass surgery, resulting in the release of metabolic and inflammatory pathways.
【學位授予單位】：青島大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R589.7;R656.6

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