| Cerebral ischemia reperfusion(CIR)is a kind of ischemic cerebrovascular disease.The mainly disease process of CIR is neurological deficit,sensorimotor dysfunction,physiological structure and function of brain tissue destruction,which increased oxidation and inflammatory lesions.Salvia miltiorrhiza is the widely used herb in clinical practice.Salvia miltiorrhiza formula granules(DC)and Salvia miltiorrhiza ultrafine powder(DP)are widely used in traditional Chinese medicine prescription preparations with the characteristics of convenient administration and portability.However,there is no relevant research report on the effect of the two preparations on the treatment of disease under the equivalent dose.This study intends to compare the protective effects of DC and DP on cerebral injury of MCAO mice.This study has divided into three parts and each part are summarized as follows.Part 1:Effect of Salvia miltiorrhiza formulation granules and Salvia miltiorrhiza powder on sensorimotor injury in mice in cerebral ischemia reperfusion injuryObjective:To observe the protective effect of Salvia miltiorrhiza formulation granules and Salvia miltiorrhiza powder on sensorimotor injury of mice in cerebral ischemia reperfusion injury.Methods:The ICR mice were divided into 4 groups randomly,that is Sham group,CIR group,CIR+DC group(0.0225 g/mL)and CIR+DP group(0.1125 g/mL).The model of mice was prepared with middle cerebral artery occlusion(MCAO)and conducted reperfusion surgery after ischemia for one hour.The impaired functional recovery of mice was evaluated with the neurological function score,corner turn test score,grip force measurement of forelimber and adhesivetape-exposing test.Results:The mice in Sham group have normal activities and neurological deficits.The neurological scores of mice in CIR group were significantly increased(P<0.01);and neurological scores of mice have been reduced after DC or DP treatment with neurological deficits have improved.The LI index of mice in CIR group increased significantly after surgery for 3 days(P<0.05 or P<0.01),and decreased with DC or DP treatment.The grip force of forelimber of mice in CIR group was significantly reduced after operation(P<0.01),and has been significantly improved after DP treatment for 7 days(P<0.01)better than CIR+DC group(P<0.01).The time for mice to sense and remove tapes were significantly longer in the CIR group(P<0.05 or P<0.01),and shorter after the administration of DC or DP.Conclusion:DC and DP have a protective effect on nerve damage and sensorimotor injury after cerebral ischemia reperfusion,and have similar strengths of the equivalent doses.It can reduce the score of neurological after cerebral ischemia reperfusion,and correct the bias of limb use in order to improve the sensory dysfunction.It can also restore the fore-limb grip of mice and improve the limb sensory motor function,in which DP has a significant recovery of grip after ischemic.Part 2:Effects of Salvia miltiorrhiza formulation granules and Salvia miltiorrhiza powder on cerebral tissue damage in cerebral ischemia reperfusion injuryObjective:To observe the protective effects of Salvia miltiorrhiza formulation granules and Salvia miltiorrhiza powder on brain tissue damage and functional impairment of mice in cerebral ischemia reperfusion injury.Methods:The ICR mice were divided into 4 groups randomly,that is Sham group,CIR group,CIR+DC group(0.0225 g/mL)and CIR+DP group(0.1125 g/mL).The model of mice was prepared with middle cerebral artery occlusion(MCAO)and conducted reperfusion surgery after ischemia for one hour.Evaluated the condition of hypoxia according to gasping duration after surgery for 24 h.The protective effects of DC and DP on mice after ischemia reperfusion surgery were evaluated with the change of body weight,mortality rate,moisture of cerebral,cerebral infarct volume and histopathological morphological changes.Results:Gasping duration of mice in Sham group was 31.40 seconds which the gasping duration in CIR mice was shortened.After DC or DP treatment,the gasping duration showed an upward trend.The mortality rate of mice in CIR group was as high as 56.5%at seventh day after surgery.After DC or DP treatment,the mortality rate of mice has decreased and the mortality rate of CIR+DC group mice was 43.5%and 47.8%in CIR+DP group.The body weight of mice in CIR group after surgery was decline(P<0.01),and stabilized after 3 days in CIR+DC group,and the body weight of mice in CIR+DP group has a significant recovery effect at 7th day after reperfusion(P<0.05).The cerebral infarct volume of mice in CIR group has been closed into 30%after surgery for 24 h to 72 h.After DC or DP treatment,the volume of infarction was significantly lower than that in CIR group(P<0.05 or P<0.01).The moisture of cerebral of CIR mice increased significantly after reperfusion(P<0.01).After treatment with DC,the moisture content has decreased significantly(P<0.05).The CIR group began to show pathological injury in the cerebral cortex tissue with degeneration of neurons and nuclear shrinkage.The pathological changes in the brain have eased after DC or DP treatment.Conclusion:DC and DP have certain improvement effects on cerebral injury and functional impairment after cerebral ischemia reperfusion,and have similar strengths of the equivalent doses.DC has a significantly improvement on cerebral edema after cerebral ischemia reperfusion.DP has a significant recovery effect on weight loss after cerebral ischemia reperfusion in mice.DC and DP can significantly reduce the cerebral infarct area and improve the pathological damage of cerebral tissue.It is shown that both of them have obvious protective effect on cerebral ischemia reperfusion injury.DC have obvious effect on improving cerebral damage and DP has a better effect on restoring ischemic state.Part 3:Effects of Salvia miltiorrhiza formulation granules and Salvia miltiorrhiza powder on oxidative damage and inflammatory reaction of mice in cerebral ischemia reperfusion injuryObjective:To observe the protective effects of Salvia miltiorrhiza formulation granules and Salvia miltiorrhiza powder on oxidative damage and inflammatory reaction of mice in cerebral ischemia reperfusion injury.Methods:The ICR mice were divided into 4 groups randomly,that is Sham group,CIR group,CIR+DC group(0.0225 g/mL)and CIR+DP group(0.1125 g/mL).The model of mice was prepared with middle cerebral artery occlusion(MCAO)and conducted reperfusion surgery after ischemia for one hour.The protective effects of drugs on oxidative damage were evaluated with MDA content,LPO content,SOD activity,CAT activity,GSH-Px activity and Nox2 expression in cerebral.The protective effects of drugs on inflammatory reaction were evaluated with TNF-α content,IL-1β content and MPO content in cerebral.Results:After DC or DP treatment,the content of MDA in cerebral tissue was decreased.The expression of LPO in cerebral tissue of CIR mice was significantly increased(P<0.05),and it has decreased with DC or DP treatment of 72 h after surgery(P<0.01).The SOD activity in the CIR group was significantly reduced after surgery for 72 h(P<0.01).After DC or DP treatment,SOD activity was significantly increased(P<0.05 or P<0.01).The expression of MDA increased significantly of 72 h after surgery in the CIR group(P<0.05).The activity of CAT in the CIR group was significantly decreased(P<0.05).It has significantly increased in CIR+DP group at the 24th hour after operation(P<0.05).The activity of GSH-Px in cerebral tissue of mice in CIR group was significantly decreased(P<0.05 or P<0.01),and have a significantly increased with DP treatment after reperfusion for 72 h(P<0.05).The expression of Nox2 in cerebral of CIR mice was significantly increased(P<0.01).Among them,the reduction of Nox2 expression in cerebral after DP treatment was more significantly decreased(P<0.05).The expression of TNF-α,IL-1β and MPO in cerebral was significantly increased in CIR group(P<0.05 or P<0.01).After administration of DC or DP,the TNF-α in cerebral was significantly decreased(P<0.05 or P<0.01).It can also significantly decrease the expression of IL-1β with DC treatment for 72th hour after surgery(P<0.05).It can also decrease the MPO expression in cerebral of CIR+DP group mice(P<0.05 or P<0.01).Conclusion:DC and DP can inhibit the occurrence of oxidative and inflammatory reactions after cerebral ischemia-reperfusion,and the equivalent doses have similar strengths.DP can significantly inhibit the expression of Nox2 and the production of reactive oxygen species in order to inhibit the occurrence of oxidation reaction.It can significantly enhance the activity of SOD,CAT and GSH-PX to increase the rate of occurrence of peroxidation and lipid metabolism,and reduce the cytotoxicity damage.DC and DP can reduce the expression of LPO significantly and the expression of MDA,thereby inhibiting its cytotoxicity to brain cerebral.DC can significantly reduce the expression of IL-1β and DP can significantly reduce the expression of MPO,both of them can significantly inhibit the expression of TNF-α in order to inhibit the occurrence of cerebral inflammatory response after cerebral ischemia reperfusion.It is shown that both of them have obvious protective effect on cerebral ischemia reperfusion injury in cerebral tissue.Both of them have significant effects in inhibiting the occurrence of oxidative and inflammatory reactions,and DP plays an important role on inhibiting the generation of reactive oxygen species and enhancing peroxidase activity. |
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