双醋瑞因对黄韧带肥厚大白兔血清炎症因子调节及肥厚黄韧带病理结构的影响

目的：观察双醋瑞因对黄韧带肥厚大白兔血清白细胞介素1、白细胞介素6、肿瘤坏死因子-α和转化生长因子-β1的影响,并且观察双醋瑞因对黄韧带肥厚病理切片中弹性纤维与胶原纤维结构变化的影响.方法：采用外科手术方法进行造模,将造模成功动物分为2组,每组45只.模型组以蒸馏水灌胃,动物组为双醋瑞因灌胃,剂量为3.8 mg·kg-1,连续干预3个月.分别于造模开始后第4周、第8周和第12周从2组各随机选取10只动物取静脉血采用ELISA法测定血清白细胞介素1、白细胞介素6、肿瘤坏死因子-α和转化生长因子-β1含量;取静脉血后处死动物,取黄韧带切片后HE染色在光镜下观察.结果：①血清指标检查结果.造模开始后第4周,2组动物血清白细胞介素1、白细胞介素6、肿瘤坏死因子-α和转化生长因子-β1含量比较,差异无统计学意义[（10.20±2.35）ng· mL-1,（9.06±2.68）ng·mL-1,t=0.021,P=0.605; （34.90±11.26）pg·mL-1,（32.50±9.35）pg· mL-1,t=0.532,P=0.182; （10.20 ±2.35）ng· mL-1,（9.06 ±2.68） ng· mL-1,t=0.021,P=0.605;（1 595.30±201.74）pg· mL-1,（1 835.20±154.36）pg·mL-1,t=0.142,P=0.236].造模开始后第8周,模型组血清白细胞介素1和肿瘤坏死因子-α含量高于药物组[（83.50±15.71）ng· mL-1,（49.70±13.58） ng·mL-1,t=3.257,P=0.000;（14.50±4.08）ng· mL-1,（12.20±3.04）ng·mL-1,t=1.273,P=0.034],转化生长因子-β1含量低于药物组[（1 862.90±284.66）pg ·mL-1,（2 306.80±325.64） pg·mL-1,t=15.384,P=0.017];2组动物血清白细胞介素6含量比较,差异无统计学意义[（39.40±13.84）pg·mL-1,（34.60±15.72）pg·mL-1,t=0.457,P=0.235].造模开始后第12周,模型组血清白细胞介素1和肿瘤坏死因子-α含量高于药物组[（58.50±16.42）ng· mL-1,（46.30±13.94）ng· mL-1,t=1.083,P =0.021;（14.20±3.56）ng· mL-1,（10.70±3.65）ng· mL-1,t=1.563,P=0.018];2组动物白细胞介素6和转化生长因子-β1含量比较,差异无统计学意义[（34.60±9.38）pg· mL-1,（33.80±12.38） pg· mL-1,t=0.183,P=0.317; （2 039.50±234.56） pg· mL-1,（2 106.40±256.34） pg· mL-1,t=1.632,P=0.538].②光镜下观察结果.造模后第4周,模型组黄韧,胶原纤维开始增生,到第8周增生最明显,第12周弹性纤维正常组织结构消失,弹性纤维排列断裂、卷曲、紊乱,数量减少,排列松散,胶原纤维增生;造模后第4周,药物组黄韧带可见胶原纤维明显增生,第8周时胶原纤维增生明显得到抑制,第12周时仅见弹性纤维少量断裂、卷曲,排列紧密,接近正常黄韧带,胶原纤维增生不明显.结论：双醋瑞因能通过抑制白细胞介素1、白细胞介素6、肿瘤坏死因子-α和转化生长因子-β1的表达,延缓黄韧带肥厚大白兔肥厚黄韧带中胶原纤维增生,并使之恢复至正常状态或接近正常状态.

Effect of Diacerein on serum inflammatory cytokines and the pathological structure of ligamentum flavum in white rabbit with hypertrophic ligamentum flavum

Objects： To investigate the effects of Diacerein on the Interleukin 1 （IL-1）,Interleukin 6 （IL-6）,Tumor Necrosis Factor α （TNF-α） and Transforming Growth Factor β1 （TGF-β1）in serum of white rabbit hypertrophic ligamentum flavum,the effects of Diacerein on the structure change of elastic fabric and collagen fabric in hypertrophic ligamentum flavum pathological section.Method： Model was made by surgeries and the rabbits were divided into 2 groups with 45 rabbits in each group.Model group was given distilled water by gavage,control group was given Diacerein with dose of 3.8 mg/kg for 3 months.Venous blood was draw from 10 rabbits in each group 4 weeks,8 weeks and 12 weeks later to measure the content of IL-1,IL-6,TNF-α and TGF-β1 by ELISA method.The ligamentum flavum was got after drawing venous blood and sectioned and HE stained for observation under light microscope.Results：There was no statistical significance in the content of IL-1,IL-6,TNF-α and TGF-β1 between the 2 groups 4 weeks after molding （（10.20 ＋/-2.35 vs 9.06 ＋/-2.68 ng/mL,t =0.021,P =0.605;34.90 ＋/-11.26 vs 32.50 ＋/-9.35 pg/mL,t =0.532,P =0.182;10.20 ＋/-2.35 vs 9.06 ＋/-2.68 ng/mL,t =0.021,P =0.605 ;1 595.30 ＋/-201.74 vs 1 835.20 ＋/-154.36 pg/mL,t =0.142,P =0.236）.The content of IL-1 and TNF-α in model group was superior to that in drug group 8 weeks after modeling（83.50 ＋/-15.71 vs 49.70 ＋/-13.58 ng/mL,t =3.257,P =0.000 ; 14.50 ＋/-4.08 vs 12.20 ＋/-3.04 ng/mL,t =1.273,P =0.034）,the content of TGF-β1 was below that in drug group （1 862.90 ＋/-284.66 vs 2 306.80 ＋/-325.64 pg/mL,t =15.384,P =0.017）.There was no statistical significance in the content of IL-6 between the two groups（39.40 ＋/-13.84 vs 34.60 ＋/-15.72 pg/mL,t =0.457,P =0.235）,the content of IL-1 and TNF-α in model group was superior to that in drug group 12 weeks after modeling（58.50 ＋/-16.42 vs 46.30 ＋/-13.94 ng/mL,t =1.083,P =0.021,（14.20 ＋/-3.56 vs 10.70 ＋/-3.65 ng/mL,t =1.563,P =0.018）.There was no statistical significance in the content of IL-6 and TGF-β1 between the two groups.The collagen fabric started proliferation in model group 4 weeks after modeling,it was most remarkable in the 8th week,normal structure of elastic fabric vanished in the 12th week and showed rupture,crimp,disorder,decline in number and loosely arranging,proliferation of collagen fabric.The proliferation of collagen fabric in ligamentum flavum was showed in drug group 4 weeks after modeling,proliferation of collagen fabric was inhibited in the 8th week,only a little elastic fabric showed rupture,crimp and it arranged tightly almost same with that in the normal ligamentum flavum was no obvious proliferation of collagen fiber.Conclusion：Diacerein could postpone the proliferation of collagen fiber in hypertrophic ligamentum flavum rabbit and make it return to normal or close to normal by inhibiting the expression of IL-1,IL-6,TNF-α and TGF-β1.