复方竹节参片对模型家兔血清炎性因子表达的影响

The effect of Fufang Zhujieshen Tablets on inflammatory factors in osteoarthritis rabbits

目的:研究复方竹节参片对骨性关节炎模型家兔的药理作用及临床意义。方法:取40只6个月左右月龄家兔随机分为A组(正常对照组)、B组(模型对照组)、C组(复方竹节参片给药组)、D组(对照药物组)。第1周全部采用正常喂养方式,第2周开始B、C、D 3组进行Hulth造模,构建家兔骨性关节炎的动物模型,术后1周内注射青霉素预防感染。C组第4周开始双氯芬酸钠灌胃,持续2周;D组第4周开始中药灌胃,持续2周。第6周开始分组进行家兔模型的心脏取血,采用放射免疫法检测其血清中白细胞介素-1(IL-1)、白细胞介素8(IL-8)、肿瘤坏死因子(TNF)水平。采用Autodock分子对接预测筛选复方竹节参片中的炎性因子靶向抑制活性成分。结果:与A组相比,B组上述各因子水平明显升高;C、D 2组与B组相比,2组上述因子水平明显下降,具有非常显著的差异(P<0.01)。C、D 2组相比差异无显著性(P>0.05)。分子对接中与阳性对照相比,26个竹节参皂苷配体、36个白芍苷和101个甘草酚与TNF的结合能低于阳性对照;18个白芍苷、26个甘草酚与IL-1的结合能低于阳性对照,20个白芍、45个甘草酚与IL-8的结合能低于阳性对照,表明这些配体分子能与IL-1或IL-8结合形成稳定的复合物从而产生疗效。结论:复方竹节参片对于模型家兔血清中炎性因子有一定的抑制作用,且与对照药物组实验数据相比差异无显著性。具有一定的临床参考价值。预测复方竹节参片处方中对TNF起主要抑制作用的成分为竹节参、对IL-1和IL-8起主要抑制作用的成分为白芍和甘草,三者协同作用于TNF、IL-1和IL-8产生治疗骨性关节炎的疗效。

OBJECTIVE To study the pharmacological effects and clinical significance of Fufang Zhujieshen Tablets on rabbits with osteoarthritis.METHODS Forty rabbits(≥6 months)were randomly divided into group A(normal control group),group B(model control group),group C(Fufang Zhujieshen Tablets group)and group D(control drug group).In the first week,All rabbits were fed with normal feeding method.In the second week,Hulth model was established in groups B,C and D.The animal model of osteoarthritis was established in rabbits..Penicillin was injected to prevent infection within 1 week post operation.In group C,diclofenac sodium was administered by gavage for 2 weeks in the 4 th week;in group D,traditional Chinese medicine was administered by gavage for 2 weeks in the 4 th week.At the 6 th week,the rabbits were divided into groups to collect blood from the heart,and the serum levels of interleukin-1(IL-1),interleukin-8(IL-8)and tumor necrosis factor(TNF)were detected by radioimmunoassay.The targeted inhibitory active ingredient in the Fufang Zhujieshen Tablets was screened by Autodock molecular docking.RESULTS Compared with group A,the levels of the above factors in group B were significantly higher.Compared with group B,the levels of these factors in group C and group D were significantly decreased with significant differences(P<0.01).There was no significant difference between groups C and D(P>0.05).Compared with the positive control,the binding energy of 26 compounds in Panar japonicus C.A.Mey.,36 compounds in Paeonia tacti lora Pall.and 101 compounds in Glycyrrhiza uralensis Fisch to TNF was lower than that of the positive control;The binding energy of 18 compounds in Paeonia tacti lora Pall.,26 compounds in Glycyrrhiza uralensis Fisch to IL-1 was lower than that of the positive control,and the binding energy of 20 compounds in Paeonia tacti lora Pall.and 45 compounds in Glycyrrhiza uralensis Fisch to IL-8 was lower than that of the positive control,indicating indicating that these ligand molecules can bind to IL-1 or IL-8 to form stable complexes and thus produce efficacy.CONCLUSION Fufang Zhujieshen Tablets have shown partial inhibitory effect on the inflammatory factors in osteoarthritis rabbits,and the effect is similar to diclofenac sodium.It is demonstrated that Fufang Zhujieshen Tablets exhibitied clinical effects.It was predicted that the main inhibitory components of TNF in the Fufang Zhujieshen Tablets were Zhujieshen,and the main inhibitory components of IL-1 and IL-8 were Paeonia lactiflora and Glycyrrhiza uralensis,all of which acted synergistically on TNF,IL-1 and IL-8 to treat osteoarthritis.