清泻浊毒法对实验性高尿酸血症和急性痛风性关节炎的影响及机理研究
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摘要
目的：探讨清泻浊毒法对高尿酸血症和急性痛风性关节炎的影响及作用机理。
方法：1.氧嗪酸钾混悬液一次性腹腔注射小鼠,制作高尿酸血症模型。2.观察清泻浊毒法对模型小鼠血尿酸及肝脏黄嘌呤氧化酶的影响。3.观察清泻浊毒法对高尿酸血症大鼠的尿量、尿尿酸浓度及尿尿酸总量的影响。4.观察清泻浊毒方对急性痛风性关节炎大鼠的步态、体重、关节肿胀度及炎症介质水平的影响。
结果：1.小鼠腹腔注射氧嗪酸钾盐后血尿酸水平明显升高,给予降尿酸药物后明显降低。2.清泻浊毒法可显著降低模型小鼠的血尿酸浓度及黄嘌呤氧化酶活性(P<0.01)。3.土茯苓熟大黄组小鼠24h尿量及尿尿酸总量最高,其次为清泻浊毒方组；土茯苓熟大黄组和苯溴马隆组尿尿酸浓度明显升高。4.急性痛风性关节炎模型组大鼠的步态呈中重度跛行,踝关节周径显著增大。造模72小时后,模型组和清泻浊毒方组的踝关节周径与造模后24小时比较均有轻度下降,而吲哚美辛组大鼠踝关节周径仍轻度增加,并且与造模前比较有显著性差异(P<0.01)。吲哚美辛组大鼠体重下降,清解浊毒方组和空白组大鼠体重增加无明显差异(P>0.05)。清泻浊毒方降低模型大鼠关节组织中升高的TNF-α、IL-1β水平,对MMP-3影响不明显,并减轻关节组织的炎性细胞浸润。
结论：1.腹腔注射氧嗪酸盐法能够成功制造动物高尿酸血症模型,并能筛选降尿酸药物；2.清泻浊毒法能够降低高尿酸血症模型小鼠的血尿酸水平,其机制可能是降低肝脏黄嘌呤氧化酶水平；3.清泻浊毒法增加模型大鼠的尿量、尿酸浓度和24h尿尿酸总量,其中土茯苓熟大黄起了主要作用；4.清泻浊毒方水煎剂能够改善急性痛风性关节炎模型大鼠的踝关节功能,减轻炎性细胞浸润,对大鼠的消化功能没有影响；降低关节组织中的TNF-α、IL-1β水平,对MMP-3影响不明显。
Objective To explore the effect and its mechanism of clearing and purging heat and turbid toxins on hyperuricemia and acute gouty arthritis.
Methods 1. Hyperuricemia model was established by intraperitoneal injection with oteracil potassium suspension.2. The effect of clearing and purging heat and turbid toxins on blood uric acid and liver xanthinoxidase of model rice was observed.3. The effect of clearing and purging heat and turbid toxins on urine volume, concentration and amount of urinary uric acid of model rats.4. The effect of clearing and purging heat and turbid toxins on gait, weight, feet swelling degree and mediators of inflammation of model rats were examined.
Results 1. Blood uric acid level of model mice increased markedly after intraperitoneal injection with oteracil potassium suspension, while decreased significantly after administration of hypouricemic drug.2. The method of clearing and purging heat and turbid toxins could decrease the concentration of blood uric acid and activity of xanthinoxidase of model mice(P<0.01).3. The urine volume and amount of urinary uric acid of the decoction of Glabrous Greenbrier Rhizome and prepared rhubarb group were the most and that of the decoction of clearing and purging heat and turbid toxins fomula group was the second. Concentration of urinary uric acid of the decoction of Glabrous Greenbrier Rhizome and prepared rhubarb group and benzbromarone group were increased markedly.4. Model rats of acute gouty arthritis limped severely and the ankle circumference of model group increase markedly.72 hours after modeling, the ankle circumference of model group and the decoction of clearing and purging heat and turbid toxins fomula group decreased slghtly, while that of indometacin group increased slightly which was significantly different from that before modeling(P<0.01). The weight of indometacin group were reduced. And there was no significant difference between the weight gaining of the blank group and the decoction of clearing and purging heat and turbid toxins fomula group(P>0.05). Both clearing and purging heat and turbid toxins fomula and indometacin could reduce the elevated level of TNF-αand IL-1βin joint tissue of model rats. While the effect of the two drugs on MMP-3 was not obvious. And the two drugs could both relieve the inflammatory cells infiltration in joint tissue of model rats.
Conclusions 1. Animal model of hyperuricemia could established by intraperitoneal injection with oteracil potassium suspension and thus helps to select hypouricemic drug.2. Blood uric acid level of model rice of hyperuricemia could be decreased by method of clearing and purging heat and turbid toxins. Its mechanism may be related to reducing the level of liver xanthinoxidase. The method of clearing and purging heat and turbid toxins could increase the level of urine volume, concentration and amount of urinary uric acid of model rats of hyperuricemia and Glabrous Greenbrier Rhizome and prepared rhubarb may play a main role.4. Decoction of clearing and purging heat and turbid toxins fomula could improve anckle joint function of model rats of Acute gouty arthritis. And it could relieve the inflammatory cells infiltration and reduce the elevated level of TNF-αand IL-1βin joint tissue of model rats. While it has no effect on digestive function of model rats and its effect on MMP-3 was not obvious.
方法：1.氧嗪酸钾混悬液一次性腹腔注射小鼠,制作高尿酸血症模型。2.观察清泻浊毒法对模型小鼠血尿酸及肝脏黄嘌呤氧化酶的影响。3.观察清泻浊毒法对高尿酸血症大鼠的尿量、尿尿酸浓度及尿尿酸总量的影响。4.观察清泻浊毒方对急性痛风性关节炎大鼠的步态、体重、关节肿胀度及炎症介质水平的影响。
结果：1.小鼠腹腔注射氧嗪酸钾盐后血尿酸水平明显升高,给予降尿酸药物后明显降低。2.清泻浊毒法可显著降低模型小鼠的血尿酸浓度及黄嘌呤氧化酶活性(P<0.01)。3.土茯苓熟大黄组小鼠24h尿量及尿尿酸总量最高,其次为清泻浊毒方组；土茯苓熟大黄组和苯溴马隆组尿尿酸浓度明显升高。4.急性痛风性关节炎模型组大鼠的步态呈中重度跛行,踝关节周径显著增大。造模72小时后,模型组和清泻浊毒方组的踝关节周径与造模后24小时比较均有轻度下降,而吲哚美辛组大鼠踝关节周径仍轻度增加,并且与造模前比较有显著性差异(P<0.01)。吲哚美辛组大鼠体重下降,清解浊毒方组和空白组大鼠体重增加无明显差异(P>0.05)。清泻浊毒方降低模型大鼠关节组织中升高的TNF-α、IL-1β水平,对MMP-3影响不明显,并减轻关节组织的炎性细胞浸润。
结论：1.腹腔注射氧嗪酸盐法能够成功制造动物高尿酸血症模型,并能筛选降尿酸药物；2.清泻浊毒法能够降低高尿酸血症模型小鼠的血尿酸水平,其机制可能是降低肝脏黄嘌呤氧化酶水平；3.清泻浊毒法增加模型大鼠的尿量、尿酸浓度和24h尿尿酸总量,其中土茯苓熟大黄起了主要作用；4.清泻浊毒方水煎剂能够改善急性痛风性关节炎模型大鼠的踝关节功能,减轻炎性细胞浸润,对大鼠的消化功能没有影响；降低关节组织中的TNF-α、IL-1β水平,对MMP-3影响不明显。
Objective To explore the effect and its mechanism of clearing and purging heat and turbid toxins on hyperuricemia and acute gouty arthritis.
Methods 1. Hyperuricemia model was established by intraperitoneal injection with oteracil potassium suspension.2. The effect of clearing and purging heat and turbid toxins on blood uric acid and liver xanthinoxidase of model rice was observed.3. The effect of clearing and purging heat and turbid toxins on urine volume, concentration and amount of urinary uric acid of model rats.4. The effect of clearing and purging heat and turbid toxins on gait, weight, feet swelling degree and mediators of inflammation of model rats were examined.
Results 1. Blood uric acid level of model mice increased markedly after intraperitoneal injection with oteracil potassium suspension, while decreased significantly after administration of hypouricemic drug.2. The method of clearing and purging heat and turbid toxins could decrease the concentration of blood uric acid and activity of xanthinoxidase of model mice(P<0.01).3. The urine volume and amount of urinary uric acid of the decoction of Glabrous Greenbrier Rhizome and prepared rhubarb group were the most and that of the decoction of clearing and purging heat and turbid toxins fomula group was the second. Concentration of urinary uric acid of the decoction of Glabrous Greenbrier Rhizome and prepared rhubarb group and benzbromarone group were increased markedly.4. Model rats of acute gouty arthritis limped severely and the ankle circumference of model group increase markedly.72 hours after modeling, the ankle circumference of model group and the decoction of clearing and purging heat and turbid toxins fomula group decreased slghtly, while that of indometacin group increased slightly which was significantly different from that before modeling(P<0.01). The weight of indometacin group were reduced. And there was no significant difference between the weight gaining of the blank group and the decoction of clearing and purging heat and turbid toxins fomula group(P>0.05). Both clearing and purging heat and turbid toxins fomula and indometacin could reduce the elevated level of TNF-αand IL-1βin joint tissue of model rats. While the effect of the two drugs on MMP-3 was not obvious. And the two drugs could both relieve the inflammatory cells infiltration in joint tissue of model rats.
Conclusions 1. Animal model of hyperuricemia could established by intraperitoneal injection with oteracil potassium suspension and thus helps to select hypouricemic drug.2. Blood uric acid level of model rice of hyperuricemia could be decreased by method of clearing and purging heat and turbid toxins. Its mechanism may be related to reducing the level of liver xanthinoxidase. The method of clearing and purging heat and turbid toxins could increase the level of urine volume, concentration and amount of urinary uric acid of model rats of hyperuricemia and Glabrous Greenbrier Rhizome and prepared rhubarb may play a main role.4. Decoction of clearing and purging heat and turbid toxins fomula could improve anckle joint function of model rats of Acute gouty arthritis. And it could relieve the inflammatory cells infiltration and reduce the elevated level of TNF-αand IL-1βin joint tissue of model rats. While it has no effect on digestive function of model rats and its effect on MMP-3 was not obvious.
引文
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