白藜芦醇对兔骨关节炎作用的实验研究
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摘要
目的:
研究白藜芦醇对兔骨关节炎(OA)模型血清、滑膜、骨关节液、关节软骨中NO和iNOS水平的影响,探讨其治疗骨关节炎的作用机制。
方法:
36只健康新西兰兔,随机抽取6只,作为正常对照组(A组)。其余30只用Hulth法复制出实验性骨关节炎模型,术后8周随机抽取6只行x线检查证实造模成功。将造模动物随机分为模型组(B组)、阳性药物组(C组,硫酸氨基葡萄糖;35 mg·kg~(-1))和白藜芦醇低剂量组(D组,白藜芦醇30 mg·(kg·d)~(-1))、中剂量组(E组,白藜芦醇60mg·(kg·d)~(-1))、高剂量组(F组,白藜芦醇120 mg·(kg·d)~(-1)),每组6只。正常组、模型组用生理盐水2ml·kg~(-1)、阳性组用硫酸氨基葡萄糖35mg·kg~(-1)、白藜芦醇低剂量组30 mg·kg~(-1)、中剂量组60 mg·kg~(-1)、高剂量组120 mg·kg~(-1)灌胃,连续给药4周后,处死动物进行以下指标检测:切取股骨内髁软骨标本,脱水,石蜡包埋后切片,用HE染色作光镜观察,按Mankin's法对关节软骨病理改变进行组织形态学评分,用硝酸还原酶法测定血清、滑膜、骨关节液中NO、iNOS含量,免疫组织化学法观察软骨细胞中iNOS阳性细胞来检测其iNOS水平。所有数据经统计学分析处理。
结果:与正常组(A组)相比,模型组(B组)兔光镜下关节软骨呈明显退行性变,Mankin's评分显著增高,模型组血清、滑膜、骨关节液中NO含量和iNOS水平显著升高(P＜0.05);给予白藜芦醇后,Mankin's评分显著降低,血清、滑膜、骨关节液中NO含量和iNOS水平显著降低(P＜0.05),D组与E组、F组之间比较差异有统计学意义(P＜0.05);C、D、E、F组软骨细胞中iNOS的阳性细胞表达率均低于B组(P＜0.05),D组与E组、F组iNOS的阳性细胞表达率之间比较差异有统计学意义(P＜0.05)。
结论:
白藜芦醇能明显降低兔骨关节炎模型血清、滑膜、骨关节液中NO和iNOS水平,降低关节软骨中iNOS的阳性表达率,有可能成为改变OA进程的有效药物。
Objective:
To study the effect of Resveratrol and possible action mechanism of Resveratrol by the determination of nitric oxide and inducible nitric oxide synthaze levels in serum,synorial membrane,joint fluids and articular cartilage in Osteoarthritis model Rabbits.
Methods:
Preparing 36 New Zealand white rabbits,and taking suction 6 rabbits randomly as the normal control group(Group A).Other rabbits are construct the osteoarthritis model rabbit above the models of doing by Hulth.After 4 weeks of operation,we confirm the building of the osteoarthritis model is successful by the alter of X-ray and pathology.And then,we take the model rabits into 5 groups:osteoarthritis model groups(Group B);positive medicament control group(Group C; glucosamine sulphate,35 mg·kg~(-1));The low dosage test medicament group(Group D;resveratrol,30 mg·(kg·d)~(-1));The middle dosage test medicament group(Group E;resveratrol,60 mg·(kg·d)~(-1));The high dosage test medicament group(Group F;resveratrol,120 mg·(kg·d)~(1-));There are 6 rabbits in each groups.Then groupA、B received stomach irritation daily with physiological saline(2ml·kg~(-1))and group D、E、F received stomach irritation daily with Resveratrol solution in different dosage for 4 weeks.Daily dosage of C、D、E、F were 35 mg·kg~(-1)、30 mg·kg~(-1)、60 mg·kg~(-1)、120 mg·kg~(-1)respectively.After 4 weeks,kill the rabbits and cutting the specimen of thighbone cartilage.Taking the specimen dehydration,embedding the specimen in paraffin and slice up.To dry with H.E.We grade the tectology with the chang of articluar cartilage by the methods of Mankin's under the microscope on the way of double blind.NO and iNOS in serum and synorial membrane and joint fluids are measured by nitrate reduction method.We detect the number of positive cells of iNOS by the methods of immuno histochemistry assay.Study the correlation between the groups by statistics analysis ways.
Result:
Compared with normal control group(group A),cartilage degradation in group is significantly less severe than that in model group(group B);The Mankin's grade in group B is higher than in group A;The levels of NO and iNOS in serum and synorial membrane and joint fluids in model group are all significantly higher than those in nomal group(P＜0.05).Gived Resveratrol,the Mankin's grade in group C、D、E、F are lower than in groupB.The levels of NO and iNOS in serum and synorial membrane and joint fluids of group C、D、E、F are significantly lower than that in the group B.(P＜0.05).Significant differences of those are found between group D and group E、F(P＜0.05).Significant differences of positive cells rates are found between group D and group E、F(P＜0.05).The positive rate of iNOS expression in chondrocyte in group C、D、E、F are significantly lower than that in group B(P＜0.05). Significant difference of positive rate of iNOS expression are found between group D and group E、F(P＜0.05).
Conclusion:
Resveratrol could reduce the expression of NO and iNOS in serum, synorial membrane and joint fluids of model rabbits.Reduce the positive rate of iNOS expression in chondrocyte.Resveratrol may be developed to be a modifying osteoarthritis drug.
研究白藜芦醇对兔骨关节炎(OA)模型血清、滑膜、骨关节液、关节软骨中NO和iNOS水平的影响,探讨其治疗骨关节炎的作用机制。
方法:
36只健康新西兰兔,随机抽取6只,作为正常对照组(A组)。其余30只用Hulth法复制出实验性骨关节炎模型,术后8周随机抽取6只行x线检查证实造模成功。将造模动物随机分为模型组(B组)、阳性药物组(C组,硫酸氨基葡萄糖;35 mg·kg~(-1))和白藜芦醇低剂量组(D组,白藜芦醇30 mg·(kg·d)~(-1))、中剂量组(E组,白藜芦醇60mg·(kg·d)~(-1))、高剂量组(F组,白藜芦醇120 mg·(kg·d)~(-1)),每组6只。正常组、模型组用生理盐水2ml·kg~(-1)、阳性组用硫酸氨基葡萄糖35mg·kg~(-1)、白藜芦醇低剂量组30 mg·kg~(-1)、中剂量组60 mg·kg~(-1)、高剂量组120 mg·kg~(-1)灌胃,连续给药4周后,处死动物进行以下指标检测:切取股骨内髁软骨标本,脱水,石蜡包埋后切片,用HE染色作光镜观察,按Mankin's法对关节软骨病理改变进行组织形态学评分,用硝酸还原酶法测定血清、滑膜、骨关节液中NO、iNOS含量,免疫组织化学法观察软骨细胞中iNOS阳性细胞来检测其iNOS水平。所有数据经统计学分析处理。
结果:与正常组(A组)相比,模型组(B组)兔光镜下关节软骨呈明显退行性变,Mankin's评分显著增高,模型组血清、滑膜、骨关节液中NO含量和iNOS水平显著升高(P＜0.05);给予白藜芦醇后,Mankin's评分显著降低,血清、滑膜、骨关节液中NO含量和iNOS水平显著降低(P＜0.05),D组与E组、F组之间比较差异有统计学意义(P＜0.05);C、D、E、F组软骨细胞中iNOS的阳性细胞表达率均低于B组(P＜0.05),D组与E组、F组iNOS的阳性细胞表达率之间比较差异有统计学意义(P＜0.05)。
结论:
白藜芦醇能明显降低兔骨关节炎模型血清、滑膜、骨关节液中NO和iNOS水平,降低关节软骨中iNOS的阳性表达率,有可能成为改变OA进程的有效药物。
Objective:
To study the effect of Resveratrol and possible action mechanism of Resveratrol by the determination of nitric oxide and inducible nitric oxide synthaze levels in serum,synorial membrane,joint fluids and articular cartilage in Osteoarthritis model Rabbits.
Methods:
Preparing 36 New Zealand white rabbits,and taking suction 6 rabbits randomly as the normal control group(Group A).Other rabbits are construct the osteoarthritis model rabbit above the models of doing by Hulth.After 4 weeks of operation,we confirm the building of the osteoarthritis model is successful by the alter of X-ray and pathology.And then,we take the model rabits into 5 groups:osteoarthritis model groups(Group B);positive medicament control group(Group C; glucosamine sulphate,35 mg·kg~(-1));The low dosage test medicament group(Group D;resveratrol,30 mg·(kg·d)~(-1));The middle dosage test medicament group(Group E;resveratrol,60 mg·(kg·d)~(-1));The high dosage test medicament group(Group F;resveratrol,120 mg·(kg·d)~(1-));There are 6 rabbits in each groups.Then groupA、B received stomach irritation daily with physiological saline(2ml·kg~(-1))and group D、E、F received stomach irritation daily with Resveratrol solution in different dosage for 4 weeks.Daily dosage of C、D、E、F were 35 mg·kg~(-1)、30 mg·kg~(-1)、60 mg·kg~(-1)、120 mg·kg~(-1)respectively.After 4 weeks,kill the rabbits and cutting the specimen of thighbone cartilage.Taking the specimen dehydration,embedding the specimen in paraffin and slice up.To dry with H.E.We grade the tectology with the chang of articluar cartilage by the methods of Mankin's under the microscope on the way of double blind.NO and iNOS in serum and synorial membrane and joint fluids are measured by nitrate reduction method.We detect the number of positive cells of iNOS by the methods of immuno histochemistry assay.Study the correlation between the groups by statistics analysis ways.
Result:
Compared with normal control group(group A),cartilage degradation in group is significantly less severe than that in model group(group B);The Mankin's grade in group B is higher than in group A;The levels of NO and iNOS in serum and synorial membrane and joint fluids in model group are all significantly higher than those in nomal group(P＜0.05).Gived Resveratrol,the Mankin's grade in group C、D、E、F are lower than in groupB.The levels of NO and iNOS in serum and synorial membrane and joint fluids of group C、D、E、F are significantly lower than that in the group B.(P＜0.05).Significant differences of those are found between group D and group E、F(P＜0.05).Significant differences of positive cells rates are found between group D and group E、F(P＜0.05).The positive rate of iNOS expression in chondrocyte in group C、D、E、F are significantly lower than that in group B(P＜0.05). Significant difference of positive rate of iNOS expression are found between group D and group E、F(P＜0.05).
Conclusion:
Resveratrol could reduce the expression of NO and iNOS in serum, synorial membrane and joint fluids of model rabbits.Reduce the positive rate of iNOS expression in chondrocyte.Resveratrol may be developed to be a modifying osteoarthritis drug.
引文
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