高尿酸模型鸡免疫器官血管活性肠肽表达和血液流变学的研究
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摘要
鸡高尿酸血症是嘌呤代谢紊乱或尿酸排泄减少所致血中尿酸水平持续增高而引起的疾病,其临床特征是痛风石形成、关节炎、肾结石、输尿管结石等。尿酸盐晶体的沉积能促使炎症细胞发生吞噬反应并释放多种致痛致炎细胞因子,从而引发全身性炎症反应。流行病学研究发现,我国笼养鸡高尿酸血症的发病率呈逐年上升的趋势,其原因主要是饲料中蛋白质和钙的含量过高以及维生素A和D的缺乏。值得关注的是许多病鸡还伴有血液流变性和尿酸代谢酶的异常。
血管活性肠肽是神经系统与免疫系统之间联系的一座桥梁,它不仅具有舒张平滑肌和扩张血管的作用还在免疫调节中扮演了重要的角色。新近研究表明,血管活性肠肽参与T、B淋巴细胞的分化成熟,促进巨噬细胞分泌抗炎因子,抑制其分泌促炎因子,从而既能扩张血管促进血尿酸的排泄又能在高尿酸血症的炎症反应中起消炎作用。因此,我们认为血管活性肠肽是一种有效的治疗鸡高尿酸血症的药物。为进一步阐明血管活性肠肽在鸡高尿酸血症中的作用,本实验通过饲喂高蛋白日粮和高钙高蛋白日粮建造鸡高尿酸动物模型,采用免疫组化SABC染色法,检测动物胸腺、脾脏、法氏囊中的血管活性肠肽的阳性分布,图像分析软件定量测定阳性细胞及神经纤维的平均光密度值,用SPSS11.5统计软件对其光密度值进行t检验分析,以研究血管活性肠肽在模型动物主要免疫器官中的分泌特点,探讨血管活性肠肽在鸡高尿酸血症中的作用,为临床治疗高尿酸血症提供新的思路。另外本实验采用生化方法检测分析造模不同阶段动物血清中尿酸代谢关键酶及血液流变学指标,为高尿酸血症发病机制及其流变学变化规律的理论研究奠定基础。
实验结果和结论如下:①饲喂高蛋白日粮与高钙高蛋白日粮可以成功建立鸡高尿酸血症模型。②免疫组化法观察到高尿酸模型鸡的胸腺、脾脏、法氏囊中各结构层血管活性肠肽阳性面积及着色强度均高于对照组动物,且差异显著(P﹤0.05)。高钙高蛋白日粮组模型鸡血管活性肠肽免疫阳性与高蛋白组相比有升高的趋势但是差异不显著(P>0.05)。生化法观察到高尿酸模型鸡在造模第14天时,黄嘌呤氧化酶、腺苷脱氨酶的活性与对照组相比差异不显著(P>0.05),鸟嘌呤脱氨酶活性显著升高(P<0.05);在造模第28天时,腺苷脱氨酶活性差异不显著(P>0.05),黄嘌呤氧化酶、鸟嘌呤脱氨酶活性显著升高(P<0.05);在造模第42天时三种酶的活性皆显著升高(P<0.05)。全血粘度在造模第14天时于200(1/s)、30(1/s)切变率下的差异不显著(P>0.05),在低切变率下显著升高(P﹤0.05);在造模第28天时于200(1/s)切变率下的差异不显著(P>0.05),在其他切变率下显著升高(P﹤0.05);在造模第42天时的各个切变率下都显著升高(P﹤0.05)。红细胞压积和血沉在造模过程中随着造模时间的延长有升高的趋势,但差异不显著(P>0.05)。红细胞变形指数从造模第28天开始显著降低(P﹤0.05)。红细胞聚集指数有升高趋势,但没有明显差异(P>0.05)。
在高尿酸血症模型鸡胸腺、脾脏、法氏囊这3个重要的免疫器官中血管活性肠肽的阳性表达显著增加,主要表现在T、B淋巴细胞、巨噬细胞及神经纤维的免疫反应强度增加,说明鸡高尿酸血症对免疫器官血管活性肠肽的合成有诱导作用,它作为一种信号肽介导了免疫器官和神经内分泌系统间的相互作用,进一步证实血管活性肠肽与鸡高尿酸血症发生发展的病理过程可能有密切关系;鸡高尿酸血症模型的病理机制可能与尿酸代谢关键酶的活性及血液流变学的变化密切相关。
Hyperuricemia is a diseases caused by purine metabolic disorders or uric acid excretion decrease.Clinical characteristics of hyperuricemia is chalk stone,arthritis,kidney stone, ureteral etc.Urate crystal deposition will impel inflammatory cells to phagocytic reaction and released several proinflammtory and algesic factors during the process of phagocytosis, thereby causing more extensive inflammation.Epidemiological studies have shown that hyperuricemia incidence is increasing trend of China's chickens kept in cages.The main reason is the feed protein and calcium content is too high, and lack of vitamins A and D.Concern is the many sick chickens with abnormal hemorheology and uric acid metabolism enzyme.
Vasoactive intestinal peptide is a bridge between the nervous system and the immune system. It ont only could relax vascular smooth muscle and dilate blood vessels but also played an important role in immunomodulation.Recent studies show, vasoactive intestinal peptide participate in T, B lymphocyte maturation, promote the secretion of macrophage inflammatory factor,inhibit the macrophages produce proinflammatory. VIP could both dilate blood vessels to promote the excretion of uric acid and take effect on anti-inflammatory in hyperuricemia inflammation.Therefore, we think VIP is the effective treatment drugs of chickens hyperuricemia. To further clarify the effect of VIP in chicken hyperuricemia, models of hyperuricemia chicken induced by high protein and high protein diets high in calcium.The expression of VIP immunopositive cells in thymus、spleen and bursa of Fabricius were deteced with immunohistochemical SABC method. The computer image analysed average optical density of VIP immunopositive cells. Disposed the data of the computer image analysis by SPSS for windows 11.5 statistical software to observe the distribution of VIP immunopositive cells and never fiber in the main immune organs of hyperuricemia chickens. Investigate the effect of VIP in chicken hyperuricemia in order to provide a new idea for clinical treatment of hyperuricemia. The changes of key enzyme and hemorheology index were tested with biochemistry method in order to investgate the athogenesis and hemorheology in the hyperuricemia chickens.
Experimental results and conclusions are as follows①The feeding of high protein diets and high protein diets high in calcium can successfully build chicken hyperuricemia model.②Observation of immunohistochemistry method:VIP expression in the immune organs were increased in the high protein diet group and high protein diets high in calcium group compared with the control group (P﹤0.05). Compared with the high protein diet group, the VIP expression in the high protein diets high in calcium group had the trend of rising,but the results showed no significant difference(P﹥0.05). Observation of biochemistry method: The activity expression of xanthine oxidase(XOD) and adenosine deaminase(ADA) on 14 days showed no significant difference compared with the contol group(P>0.05).That of guanosine deaminase(GD) were increased obviously on 14 days(P﹤0.05). The activity expression of ADA on 28 days showed no significant difference(P>0.05).That of XOD、GD were increased obviously on 28 days(P﹤0.05). The activity expression of XOD、ADA、GD were increased obviously on 42 days(P﹤0.05). The whole blood viscosity increased significantly on 14 and 28 days at lower shear rate in the disease of hyperuricemia.(P﹤0.05),that increased significantly at every shear rate on 42 days(P﹤0.05). Hematocrit and erythrocyte sedimentation had the trend of rising , but those elements showed no obviously different compared with that of contol group(P﹥0.05).Erythrocyte deformation index decreased obviously on 28 days (P﹤0.05). Erythrocyte aggregation index had the trend of rising,but the result showed on significant difference(P﹥0.05).
The expression of VIP in thymus,spleen and bursa of Fabricius were increased .The increasing density and degree of immumstaining is manifested mainly in T cell,B cell,macrophage and never fiber.It can be seen that hyperuricemia could induce immune organ to produce VIP. VIP might mediate immune system interaction with neuroendocrine system as a kind of signal peptide and was involved in chickens hyperuricemia.The athogenesis of hyperuricemia in chicken may be associated with VIP,the active of key enzyme and the changes of hemorheology.
血管活性肠肽是神经系统与免疫系统之间联系的一座桥梁,它不仅具有舒张平滑肌和扩张血管的作用还在免疫调节中扮演了重要的角色。新近研究表明,血管活性肠肽参与T、B淋巴细胞的分化成熟,促进巨噬细胞分泌抗炎因子,抑制其分泌促炎因子,从而既能扩张血管促进血尿酸的排泄又能在高尿酸血症的炎症反应中起消炎作用。因此,我们认为血管活性肠肽是一种有效的治疗鸡高尿酸血症的药物。为进一步阐明血管活性肠肽在鸡高尿酸血症中的作用,本实验通过饲喂高蛋白日粮和高钙高蛋白日粮建造鸡高尿酸动物模型,采用免疫组化SABC染色法,检测动物胸腺、脾脏、法氏囊中的血管活性肠肽的阳性分布,图像分析软件定量测定阳性细胞及神经纤维的平均光密度值,用SPSS11.5统计软件对其光密度值进行t检验分析,以研究血管活性肠肽在模型动物主要免疫器官中的分泌特点,探讨血管活性肠肽在鸡高尿酸血症中的作用,为临床治疗高尿酸血症提供新的思路。另外本实验采用生化方法检测分析造模不同阶段动物血清中尿酸代谢关键酶及血液流变学指标,为高尿酸血症发病机制及其流变学变化规律的理论研究奠定基础。
实验结果和结论如下:①饲喂高蛋白日粮与高钙高蛋白日粮可以成功建立鸡高尿酸血症模型。②免疫组化法观察到高尿酸模型鸡的胸腺、脾脏、法氏囊中各结构层血管活性肠肽阳性面积及着色强度均高于对照组动物,且差异显著(P﹤0.05)。高钙高蛋白日粮组模型鸡血管活性肠肽免疫阳性与高蛋白组相比有升高的趋势但是差异不显著(P>0.05)。生化法观察到高尿酸模型鸡在造模第14天时,黄嘌呤氧化酶、腺苷脱氨酶的活性与对照组相比差异不显著(P>0.05),鸟嘌呤脱氨酶活性显著升高(P<0.05);在造模第28天时,腺苷脱氨酶活性差异不显著(P>0.05),黄嘌呤氧化酶、鸟嘌呤脱氨酶活性显著升高(P<0.05);在造模第42天时三种酶的活性皆显著升高(P<0.05)。全血粘度在造模第14天时于200(1/s)、30(1/s)切变率下的差异不显著(P>0.05),在低切变率下显著升高(P﹤0.05);在造模第28天时于200(1/s)切变率下的差异不显著(P>0.05),在其他切变率下显著升高(P﹤0.05);在造模第42天时的各个切变率下都显著升高(P﹤0.05)。红细胞压积和血沉在造模过程中随着造模时间的延长有升高的趋势,但差异不显著(P>0.05)。红细胞变形指数从造模第28天开始显著降低(P﹤0.05)。红细胞聚集指数有升高趋势,但没有明显差异(P>0.05)。
在高尿酸血症模型鸡胸腺、脾脏、法氏囊这3个重要的免疫器官中血管活性肠肽的阳性表达显著增加,主要表现在T、B淋巴细胞、巨噬细胞及神经纤维的免疫反应强度增加,说明鸡高尿酸血症对免疫器官血管活性肠肽的合成有诱导作用,它作为一种信号肽介导了免疫器官和神经内分泌系统间的相互作用,进一步证实血管活性肠肽与鸡高尿酸血症发生发展的病理过程可能有密切关系;鸡高尿酸血症模型的病理机制可能与尿酸代谢关键酶的活性及血液流变学的变化密切相关。
Hyperuricemia is a diseases caused by purine metabolic disorders or uric acid excretion decrease.Clinical characteristics of hyperuricemia is chalk stone,arthritis,kidney stone, ureteral etc.Urate crystal deposition will impel inflammatory cells to phagocytic reaction and released several proinflammtory and algesic factors during the process of phagocytosis, thereby causing more extensive inflammation.Epidemiological studies have shown that hyperuricemia incidence is increasing trend of China's chickens kept in cages.The main reason is the feed protein and calcium content is too high, and lack of vitamins A and D.Concern is the many sick chickens with abnormal hemorheology and uric acid metabolism enzyme.
Vasoactive intestinal peptide is a bridge between the nervous system and the immune system. It ont only could relax vascular smooth muscle and dilate blood vessels but also played an important role in immunomodulation.Recent studies show, vasoactive intestinal peptide participate in T, B lymphocyte maturation, promote the secretion of macrophage inflammatory factor,inhibit the macrophages produce proinflammatory. VIP could both dilate blood vessels to promote the excretion of uric acid and take effect on anti-inflammatory in hyperuricemia inflammation.Therefore, we think VIP is the effective treatment drugs of chickens hyperuricemia. To further clarify the effect of VIP in chicken hyperuricemia, models of hyperuricemia chicken induced by high protein and high protein diets high in calcium.The expression of VIP immunopositive cells in thymus、spleen and bursa of Fabricius were deteced with immunohistochemical SABC method. The computer image analysed average optical density of VIP immunopositive cells. Disposed the data of the computer image analysis by SPSS for windows 11.5 statistical software to observe the distribution of VIP immunopositive cells and never fiber in the main immune organs of hyperuricemia chickens. Investigate the effect of VIP in chicken hyperuricemia in order to provide a new idea for clinical treatment of hyperuricemia. The changes of key enzyme and hemorheology index were tested with biochemistry method in order to investgate the athogenesis and hemorheology in the hyperuricemia chickens.
Experimental results and conclusions are as follows①The feeding of high protein diets and high protein diets high in calcium can successfully build chicken hyperuricemia model.②Observation of immunohistochemistry method:VIP expression in the immune organs were increased in the high protein diet group and high protein diets high in calcium group compared with the control group (P﹤0.05). Compared with the high protein diet group, the VIP expression in the high protein diets high in calcium group had the trend of rising,but the results showed no significant difference(P﹥0.05). Observation of biochemistry method: The activity expression of xanthine oxidase(XOD) and adenosine deaminase(ADA) on 14 days showed no significant difference compared with the contol group(P>0.05).That of guanosine deaminase(GD) were increased obviously on 14 days(P﹤0.05). The activity expression of ADA on 28 days showed no significant difference(P>0.05).That of XOD、GD were increased obviously on 28 days(P﹤0.05). The activity expression of XOD、ADA、GD were increased obviously on 42 days(P﹤0.05). The whole blood viscosity increased significantly on 14 and 28 days at lower shear rate in the disease of hyperuricemia.(P﹤0.05),that increased significantly at every shear rate on 42 days(P﹤0.05). Hematocrit and erythrocyte sedimentation had the trend of rising , but those elements showed no obviously different compared with that of contol group(P﹥0.05).Erythrocyte deformation index decreased obviously on 28 days (P﹤0.05). Erythrocyte aggregation index had the trend of rising,but the result showed on significant difference(P﹥0.05).
The expression of VIP in thymus,spleen and bursa of Fabricius were increased .The increasing density and degree of immumstaining is manifested mainly in T cell,B cell,macrophage and never fiber.It can be seen that hyperuricemia could induce immune organ to produce VIP. VIP might mediate immune system interaction with neuroendocrine system as a kind of signal peptide and was involved in chickens hyperuricemia.The athogenesis of hyperuricemia in chicken may be associated with VIP,the active of key enzyme and the changes of hemorheology.
引文
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