苍柏袪痛胶囊对复合动物模型的药效学研究
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摘要
目的在高尿酸血症合并急性痛风性关节炎动物模型上,研究苍柏袪痛胶囊的药理作用。方法采用氧嗪酸钾制备高尿酸血症小鼠模型;氧嗪酸钾+Coderre法制备高尿酸血症合并急性痛风性关节炎大鼠模型。动物随机分为空白对照组、模型组、阳性对照组和苍柏袪痛胶囊组。灌胃给药结束后,测定血清中尿酸、肝脏/肾脏内的黄嘌呤氧化酶活性和关节滑膜中白细胞介素1β和金属基质蛋白酶-3的含量。采用HE染色法,观察肝、肾组织结构的病理变化。结果在2个动物模型上,苍柏袪痛胶囊均可有效降低高尿酸水平(P<0.01)和肝脏内黄嘌呤氧化酶活性(P<0.05,P<0.01)。在高尿酸血症合并急性痛风性关节炎大鼠模型上苍柏袪痛胶囊还可降低关节滑膜内的白细胞介素1β和金属基质蛋白酶-3含量。HE染色显示,苍柏袪痛胶囊可缓解高尿酸引起的肝脏炎性变化和肾实质损伤。结论苍柏袪痛胶囊具有良好的降尿酸、抗炎作用,并具有一定的肝肾保护作用。
Objective To observe the pharmacological action of Cangbai Qutong capsules on acute gouty arthritis complicated with hyperuricemia using animal models.Methods Oxonate was used by intraperitoneal injection to prepare an animal model of hyperuricemia.Both oxonate and sodium urate were given to prepare a rat model of acute gouty arthritis with hyperuricemia.All the animals were divided into different groups that were given water,allopurinol positive control drug and Cangbai Qutong capsules respectively.At the end of drug administration,the uric acid(UA)level in serum,xanthine oxidase(XOD)activity in the liver/kidney and interleukin-1β(IL-1β)and matrix metalloproteinase-3(MMP-3)in joint tissues were determined.The liver and kidney were stained with hematoxylin and eosin(H&E)to observe pathological changes.Results In both models,Cangbai Qutong capsules reduce UA levels in blood significantly(P <0.01),and inhibited XOD activity in the liver(P <0.05,P <0.01).Meanwhile,Cangbai Qutong capsules reduced the contents of IL-1βand MMP-3 in joint tissues in the rat model of acute gouty arthritis with hyperuricemia.HE showed that Cangbai Qutong capsules had a catabatic effect on liver inflammatory injury and kidney injury induced by hyperuricemia.Conclusion Cangbai Qutong capsules not only have anti-trioxypurine and anti-inflammatory effects,but can protect the liver/kidney to some extent.
Objective To observe the pharmacological action of Cangbai Qutong capsules on acute gouty arthritis complicated with hyperuricemia using animal models.Methods Oxonate was used by intraperitoneal injection to prepare an animal model of hyperuricemia.Both oxonate and sodium urate were given to prepare a rat model of acute gouty arthritis with hyperuricemia.All the animals were divided into different groups that were given water,allopurinol positive control drug and Cangbai Qutong capsules respectively.At the end of drug administration,the uric acid(UA)level in serum,xanthine oxidase(XOD)activity in the liver/kidney and interleukin-1β(IL-1β)and matrix metalloproteinase-3(MMP-3)in joint tissues were determined.The liver and kidney were stained with hematoxylin and eosin(H&E)to observe pathological changes.Results In both models,Cangbai Qutong capsules reduce UA levels in blood significantly(P <0.01),and inhibited XOD activity in the liver(P <0.05,P <0.01).Meanwhile,Cangbai Qutong capsules reduced the contents of IL-1βand MMP-3 in joint tissues in the rat model of acute gouty arthritis with hyperuricemia.HE showed that Cangbai Qutong capsules had a catabatic effect on liver inflammatory injury and kidney injury induced by hyperuricemia.Conclusion Cangbai Qutong capsules not only have anti-trioxypurine and anti-inflammatory effects,but can protect the liver/kidney to some extent.
引文
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[5]吕军,吕芳,方和金,等.高尿酸血症并急性痛风性关节炎模型的建立[J].中国现代医学杂志,2013,23(27):11-16
[6]Deng J,Lin W,Chen Y,Wang X,et al.rs3806268of NLRP3gene polymorphism is associated with the development of primary gout[J].Int J Clin Exp Pathol,2015,8(10):13747-13752
[7]Zhang B,Sun Y,Li Y,et al.Association analysis between genetic variants in interleukin genes among different populations withhyperuricemia in Xinjiang Autonomous Region[J].Int J Clin Exp Pathol,2015,8(10):13432-13440
[8]朱深银,周远大,杜冠华.防治痛风药物的研究进展[J].医药导报,2006,25(8):803-806
[9]Joosten LA,Crian TO,Azam T,et al.Alpha-1-anti-trypsinFc fusion protein ameliorates gouty arthritis by reducing release and extracellular processing of IL-1βand by the induction of endogenous IL-1Ra[J].Ann Rheum Dis,2016,75(6):1219-1227
[10]Wang P,Ren D,Chen Y,et al.Effect of sodium alginate addition to resveratrol on acute gouty arthritis[J].Cell Physiol Biochem,2015,36(1):201-207
[11]Lee J,Lee SY,Lee J,et al.Monosodium urate crystalinduced triggering receptor expressed on myeloid cells 1is associated withacute gouty inflammation[J].Rheumatology(Oxford),2016,55(1):156-161
[12]Ma MJ,Liu HC,Qu XQ,et al.Matrix metalloproteinase-3gene polymorphism and its mRNA expression in rheumatoid arthritis[J].Genet Mol Res,2015,14(4):15652-15659
[13]Yang SD,Yang DL,Sun YP,et al.17beta-estradiol protects against apoptosis induced by interleukin-1beta in rat nucleus pulposus cells by down-regulating MMP-3and MMP-13[J].Apoptosis,2015,20(3):348-357
[2]林颖达,朱小霞,薛愉,等.痛风研究进展[J].内科理论与实践,2011,6(5):379-386
[3]Hasselbacher P.Binding of IgG and complement protein monosodium urate monohydrate and other crystals[J].J Lab Clin Med,1979,94(4):532
[4]余雄英,周军,唐科,等.茶树根提取物对高尿酸血症小鼠的影响[J].中国实验方剂学杂志,2012,18(3):193-194
[5]吕军,吕芳,方和金,等.高尿酸血症并急性痛风性关节炎模型的建立[J].中国现代医学杂志,2013,23(27):11-16
[6]Deng J,Lin W,Chen Y,Wang X,et al.rs3806268of NLRP3gene polymorphism is associated with the development of primary gout[J].Int J Clin Exp Pathol,2015,8(10):13747-13752
[7]Zhang B,Sun Y,Li Y,et al.Association analysis between genetic variants in interleukin genes among different populations withhyperuricemia in Xinjiang Autonomous Region[J].Int J Clin Exp Pathol,2015,8(10):13432-13440
[8]朱深银,周远大,杜冠华.防治痛风药物的研究进展[J].医药导报,2006,25(8):803-806
[9]Joosten LA,Crian TO,Azam T,et al.Alpha-1-anti-trypsinFc fusion protein ameliorates gouty arthritis by reducing release and extracellular processing of IL-1βand by the induction of endogenous IL-1Ra[J].Ann Rheum Dis,2016,75(6):1219-1227
[10]Wang P,Ren D,Chen Y,et al.Effect of sodium alginate addition to resveratrol on acute gouty arthritis[J].Cell Physiol Biochem,2015,36(1):201-207
[11]Lee J,Lee SY,Lee J,et al.Monosodium urate crystalinduced triggering receptor expressed on myeloid cells 1is associated withacute gouty inflammation[J].Rheumatology(Oxford),2016,55(1):156-161
[12]Ma MJ,Liu HC,Qu XQ,et al.Matrix metalloproteinase-3gene polymorphism and its mRNA expression in rheumatoid arthritis[J].Genet Mol Res,2015,14(4):15652-15659
[13]Yang SD,Yang DL,Sun YP,et al.17beta-estradiol protects against apoptosis induced by interleukin-1beta in rat nucleus pulposus cells by down-regulating MMP-3and MMP-13[J].Apoptosis,2015,20(3):348-357