Inflammatory Factors Changes After Focal Cerebral Ischemia-Reperfusion In Rats And The Influence Of The Complexus Of Radix Salviae Miltiorrzhizae And Ligustrazin

Objective: To observe the influence of the complexus of Radix Salviae Miltiorrzhizae and Ligustrazin(Shenxiong Injection) on the rats'behavioral changes,Cerebral infarct volume, hemorheology and histopathology changes after focal cerebral ischemia-reperfusion, as well as to explore neuroprotective effects of Shenxiong Injection.Methods : Rats models of focal cerebral ischemia(1 hour)-reperfusion(MCAI/R)were made by using suture. Thirty three MCAI/R-established male SD rats were divided randomly into four groups,namely:the sham-operated group(6 rats), control group(9 rats), Ligustrazin-treated group(9 rats) and Shenxiong Injection-treated group(9 rats).Zea Longa's score(5 points) was introduced to evaluate behavioral changes and the 2,3,5-Triphenyl Tetrazolium Chloride(TTC) staining was applied to show cerebral infarction.The indexes of hemorheology was sampled at I1hR24h. The ultrastructure at the edge of ischemic area was observed under the electron microscope at I1hR24h.Result: The successful model ratio reached 58.5% ;Zea Longa evaluation showed no significant difference among Shenxiong Injection-treated group, Ligustrazin-treated group and control group at both I1hR6h and I1hR24h,only in Shenxiong Injection-treated group, there was significant difference between I1hR6h and I1hR24h(t test,P <0.05);Compared with control group,cerebral infarct volume in Shenxiong Injection-treated group and Ligustrazin-treated group decreased significantly(P<0.05),but there was no significant difference between Shenxiong Injection-treated group and Ligustrazin-treated group;The blood showed pathologic change of mucosity, thickness and aggregation in the MCAI/R rats, The indexes of hemorheology was improved significantly in Shenxiong Injection-treated group(P<0.01 or P<0.05),which was better than the effect of Ligustrazin. The severity of neuron damage both in Shenxiong Injection-treated group and Ligustrazin-treated group was reduced more significantly than that in the control groups(P<0.05);The neuron changes of ultrastructure in the ischemic margin were lighter in the Shenxiong Injection-treated group than those in the control groups under the electron microscope,and it was better than the Ligustrazin-treated group.Conclusion: The rat model of MCAI/R established by using suture was relatively stable, and the ratio of successful model was about 60%. Shenxiong Injection may have neuroprotective effcts on cerebral ischemia damage induced by focal cerebral ischemia-reperfusion in rats.Part 2. Effects of the complexus of Radix Salviae Miltiorrzhizae and Ligustrazin on the inflammatory factors changes after Focal Cerebral Ischemia-Reperfusion in RatsObjective: To investigate the expression of NF-κB,TNF-α,ICAM-1 in rats'brain tissue and the sequential changes of serum IL-1β,IL-6,IL-10 after focal cerebral ischemia-reperfusion,as well as to observe the influence of the complexus of Radix Salviae Miltiorrzhizae and Ligustrazin(Shenxiong Injection).Methods: Fifty four male rats were randomly divided into three groups ,namely:control group, Ligustrazin-treated group and Shenxiong Injection-treated group.Rats models of focal cerebral ischemia-reperfusion(MCAI/R)were made by using suture. 1 hour after the blood supply were blocked,drew back sutures.A series of brain and blood samples were obtained directly 6,12 and 24 hours respectively after reperfusion in three groups. The expression of NF-κB,TNF-α,ICAM-1 in the brain tissue was determined by immuno-histochemical method;Serum levels of IL-1β,IL-6,IL-10 were measured by enzyme linked immunosorbent assay (ELISA). Result: As time of I/R prolonged, The expression of TNF-α,ICAM-1 upregulated,but NF-κB reached the maximum at R12h in three groups. Compared with control group,The expression of NF-κB,TNF-α,ICAM-1 in Shenxiong-treated group decreased significantly(t test,P<0.05 ) ,which was better than the effect of Ligustrazin;Compared with Ligustrazin-treated group ,The expression of TNF-α,ICAM-1 in Shenxiong-treated group decreased significantly(P<0.05)at R24h.As time of I/R prolonged, Serum levels of IL-1β,IL-6 increased in control group and Ligustrazin-treated group, but IL-6 reached the maximum at R12h in Shenxiong-treated group.Shenxiong reduced serum levels of IL-1β,IL-6(P<0.05 or P<0.01),and increased serum levels of IL-10(P<0.05 or P<0.01). Compared with Ligustrazin-treated group, Serum levels of IL-6 in Shenxiong-treated group was higher(P<0.01)at R12h,but lower at R24h(P<0.01); Serum levels of IL-10 in Shenxiong-treated group was higher at R6h, R12h, R24h(P<0.05 or P<0.01).Conclusion: The expression of the inflammatory factors may be suppressed by Shenxiong injection with less cerebral I/R Injury, which was better than the effect of Ligustrazin alone.