| Zu Shima(Daphne)acrid,bitter,warm;a small poison;to the liver meridian which has the effect of removing wind and dehumidifying,relieving pain and dispersing blood stasis.Zu Shima is the main treatment for rheumatic arthritis,sciatica,rheumatoid arthritis,bronchitis,limb arthralgia,headache,stomachache,and hit injury.The purpose of this study is to determine the pharmacological effects of Zu Shima enteric preparation and to provide an experimental basis for its clinical application.1 The effect of Zu Shima enteric preparation on CCI ratsAim:Explore the effects of Zu Shima enteric preparation on thermal withdrawal threshold(TWT)?mechanical withdrawal threshold(MWT)and ATP family type 2 receptor(P2X4)and P38 mitogen activated protein kinase(P38MAPK)receptor in spinal cord and dorsal root ganglion(DRG)were studied in sciatic nerve chronic constriction nerve injury model(CCI)rat.Then explore the mechanism of Zushima enteric preparation in the treatment of sciatica.Methods:The right sciatic nerve of the rat was ligated to copy the model of chronic crush nerve injury.Eighth days after the operation,the random allocation method was divided into 10 groups according to the MWT value.Such as control group,sham group,model group,ibuprofen group,Zu Shima tablets 1.584,0.792,0.396g/kg group,Zu Shima enteric preparation 1.584,0.792,0.396g/kg group.Star gavage administration on the eighth day,monitoring changes of TWT,MWT during drug delivery.Perfusing and sampling after 14 days of administration,make the Immunohistochemical section of spinal cord and DRG and observe the expression of P2X4 and P38MAPK.Result:(1)TWT value:From the beginning of 8D,compared with the control group,the rats in the model group had the symptoms of heat pain sensitive(P<0.01);Compared with the model group,the TWT value of each group was reduced,and there was a significant difference(P<0.01).(2)MWT value:From the beginning of 8D;compared with the control group,the rats in the model group had the symptoms of mechanical pain sensitivity(P<0.01);From the 8D to the 14d,compared with the model group,the MWT value of each group was reduced,and there was a significant difference(P<0.01).(3)Immunohistochemical analysis of spinal cord:Compared with the control group,the P38MAPK and P2X4 receptor AOD in the dorsal horn of the spinal cord in the model group increased significantly(P<0.01);Compared with the model group,each dosage group except Zu Shima tablets 0.792g/kg group,other groups of P38MAPK,P2X4 positive expression of AOD was significantly decreased(P<0.05 or P<0.01).(4)Immunohistochemical analysis of DRG:Compared with the control group,the number of P38MAPK and P2X4 receptor positive cells in DRG increased significantly in the model group(P<0.01).Compared with the model group,the positive drug group and Zu Shima enteric preparation of 1.594g/kg group,the number of positive cells of P38MAPK receptor expression in DRG was significantly decreased in other groups(P<0.05 or P<0.01),the expression of P2X4 receptor positive cells in DRG group were significantly decreased(P<0.01).Conclusion:Zu Shima enteric preparation has a significant inhibitory effect on sciatica caused by the ligature of the sciatic nerve.The inhibitory effect of Zu Shima enteric preparation and Zu Shima tablets on sciatica induced by ligating the sciatic nerve has no significant difference.The analgesic effect of Zu Shima enteric preparation is related to the inhibition of P2X4 and P38MAPK protein expression.2 The effect of Zu Shima enteric preparation on AIA ratsAim:To study the effects of Zu Shima enteric preparation on AIA rat paw swelling rate(FSR),TWT,MWT and ELISA serum index and histopathology,explore the intervention effect of Zu Shima enteric preparation for rheumatoid arthritis.Method:After intradermal injection of Freund's complete adjuvant in the toe of the rat that were divided into 9 groups,such as control group,model group,ibuprofen group,Zu Shima tablets 1.584,0.792,0.396g/kg group,Zu Shima enteric preparation 1.584,0.792,0.396g/kg group.Star gavage administration on the second day,12 days of continuous administration.Three indexes of FSR,TWT and MWT in AIA rats were measured at seventh and twelfth days.Blood,ankle,and knee joints were taken one day after the last Administration.Enzyme linked immunosorbent assay(ELISA)was used to detect the contents of IL-6,TNF-,PGE-2,IL-10 and TGF-beta in serum.The pathological changes of ankle joint and knee joint were observed under optical microscope.Result:(1)FSR:Compared with the control group,there were significant differences between the seventh and twelfth days in the model group(P<0.01);Compared with the model group,there were significant differences in the twelfth days of each drug group(P<0.01).(2)TWT:Compared with the control group,there were significant differences between the seventh and twelfth days in the model group(P<0.01);Compared with the model group,there was significant difference between the seventh days and the twelfth days of each drug group(P<0.01).(3)MWT:Compared with the control group,there were significant differences between the seventh and twelfth days in the model group(P<0.01);Compared with the model group,there was significant difference between the seventh days and the twelfth days of each drug group(P<0.01).(4)Serum biochemical indexes:Compared with the normal group,the content of IL-6,TNF-a,PGE-2,IL-10 and TGF-beta in the serum of model rats increased significantly(P<0.01).Compared with the model group,except Zu Shima enteric preparation in 1.584g/kg group,the content of IL-6 in other groups decreased significantly(P<0.05 or P<0.01);In addition to Zu Shima tablets 0.396g/kg group and 0.396g/kg group of Zushima enteric preparation,the content of other groups decreased significantly TNF-alpha(P<0.01);In addition,Zu Shima tablets 0.792,0.396g/kg group,the content of PGE-2 in other groups decreased significantly(P<0.05 or P<0.01);The content of IL-10 in each administration group decreased significantly(P<0.01);In addition to Zushima tablets and enteric preparation of 0.396g/kg group,the content of the rest of the group TGF-beta was significantly lower(P<0.05).(5)histopathological observation:Compared with the normal group,the blood vessels of the ankle joint and the knee joint connective tissue in model group were significantly congested,inflammatory cells infiltration was obvious,synovial layer was thickened and eroded seriously,and cartilage layer and bone parenchyma were destroyed;Compared with the model group,there was significant improvement in each drug delivery group,slight congestion in connective tissue,occasional infiltration of inflammatory cells,smooth synovial layer,complete structure of cartilage and bone parenchyma.Conclusion:Zu Shima enteric preparation can significantly inhibited the swelling of rats AIA arthritis.Zu Shima enteric preparation can obviously inhibit the pain induced by Freund's complete adjuvant.Zu Shima enteric preparation has anti-inflammatory effect on rheumatoid arthritis model.3 The effect of Zu Shima enteric preparation on CIA ratsAim:To study the effect of Zu Shima enteric preparation on CIA rats,arthritis index(AI)and ELISA serum index and histopathology,explore the anti immune effect of Zushima enteric preparation for rheumatoid arthritis.Method:The two dose of bovine II collagen(BCII)emulsifier was injected into the base of the tail to make a model of rheumatoid arthritis.According to AI score random allocation method,9 groups(n= 12),such as control group,model group,ibuprofen group,ZuShima tablets 1.584,0.792,0.396g/kg group,Zu Shima enteric preparation 1.584,0.792,0.396g/kg group,10 days of continuous administration.The AI score was performed every two days.Blood,ankle,and knee joints were taken one day after the last administration.The content of IL-6,TNF-,PGE-2,COX-2,CTGF,IgG and RF in serum was detected by ELISA.A special staining of the ankle and knee joints was performed,and the damage was graded under light microscope.Result:(1)AI score:Compared with the normal group,the AI score in the model group was significantly different during the period of Administration(P<0.01);Compared with the model group,administered for tenth days,in addition to Zushima enteric preparation in 0.396g/kg group,the other groups of AI score had significantly decreased(P<0.05 or P<0.01).(2)Serum biochemical indexes:Compared with the control group,the content of IL-6,TNF-a,PGE-2,COX-2,CTGF,IgG and RF in the serum of model rats increased significantly(P<0.01 or P<0.05).Compared with the model group,the content of the other indexes was significantly different(P<0.05 or P<0.01)except the content of TNF-?;There are some differences in the content of Zushima tablet group only 1.584g/kg group CTGF,IgG,RF(P<0.05),there are differences in the concentration of COX-2 0.792 and 0.396g/kg in the group(P<0.05);There are differences between the three different contents of Zu Shima tablets three dose groups IL-6,PGE(P<0.05 or P<0.01),TNF-a difference only in group 1.584g/kg(P<0.05).Compared with the model group,there was no significant difference between the content of Zu Shima enteric preparation of three dose groups of COX-2,CTGF,IgG,RF(P>0.05);There was significant difference in the content of IL-6 and TNF-a in group 1.584 and 0.792g/kg(P<0.01);There was a significant difference in the content of PGE-2 in the only 1.584g/kg group(P<0.01).(3)Ankle joint pathological score:Compared with the control group,the ankle joint score of the model group was significantly different(P<0.01);Compared with the model group,after 10 days of administration,the scores of each group were significantly decreased(P<0.05 or P<0.01).(4)Histopathological score of knee joint synovium:Compared with the control group,the knee joint synovium score of the model group was significantly different(P<0.01);Compared with the model group,after 10 days of treatment,each group except Zu Shima tablets 0.792g/kg group and Zu Shima enteric preparation 0.396g/kg group,other groups of synovial pathological score was significantly lower(P<0.05 or P<0.01).Conclusion:Zu Shima enteric preparation has a certain inhibitory effect on articular redness caused by rheumatoid arthritis.Zu Shima enteric preparation treatment of rheumatoid arthritis is related to its anti-inflammatory effects. |
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