SheXiang Tongxin Dropping Pill Protects Against Sodium Laurate Induced Coronary Microcirculatory Dysfunction In Rats

Objective:Investigation of protective effects of SheXiang Tongxin Dropping Pill(STOP)in a rat model of coronary microcirculatory dysfunction(CMD).Methods:CMD model of SD rats was established by intraventricular injection of sodium laurate.Sixty male Sprague-Dawley rats aged 6-8 weeks were randomly divided into 4 groups:sham operation group,model group(sodium laurate),experimental group(sodium Iaurate+STDP),Positive control group(sodium laurate+nicorandil).Shexiang Tongxin Dropping Pills(STDP)and nicorandil were administered to the experimental group and the positive control group for 4 weeks before modeling.Four weeks later,the CMD model was constructed by injecting sodium laurate(0.2 mL,2 g/L)into the left ventricle of SD rats while opening the chest and clamping the aortic arch for 30 seconds.After 24 hours of surgery,the following experiments were performed:automatic biochemical analyzer was used to detect the levels of Cardiac Troponin T(cTnT),Lactic Dehydrogenase(LDH),and Creatine Kinase-MB(CK-MB)levels of all SD rats;Nitric Oxide(NO)level in SD rats of each group was detected by nitrate reductase method;serum Endothelin-1(ET-1)level in SD rats was detected by radioimmunoassay;Enzyme-Linked Immunosorbent Assay(ELISA)was used to detect serum Tumor Necrosis Factor-a(TNF-a),Interleukin--1β(IL-1β),Interleukin-6(IL-6)levels of all SD rats;oxidative stress kits for detection of serum Superoxide Dismutase(SOD)and Malonaldehyde(MDA)levels of all SD rats;Haematoxylin and Eosin staining(HE)was performed to observe the inflammatory infiltration of myocardial tissue,and Heidenhain staining to observe the ischemic necrosis of myocardial tissue;Carstairs staining was used to observe the coronary microvascular embolism.Western blotting(WB)was used to detect the expression levels of NF-κB p65,TNF-α,IL-1β,and IL-6,and caspase-3,B cell lymphoma-2(B-cell lymphoma-2,Bcl-2),Bcl-2 associated X protein(Bax)in SD rat myocardium.Results:The rat CMD model was successfully established by injecting sodium laurate into the left ventricle of SD rats.The automatic biochemical analyzer demonstrated that STDP pretreatment can significantly decrease the serum levels of cTnT,LDH,and CK-MB in CMD rats(P<0.05).Serum ET-1 level in CMD rats was significantly decreased,while NO level increased(P<0.05).STDP decreased serum levels of TNF-α,IL-1β,and IL-6 in CMD rats(P<0.05).STDP can significantly reduce the level of SOD and increase the level of MDA(P<0.05).Histopathological staining showed that STDP pretreatment reduced myocardial inflammatory infiltration,myocardial ischemia and coronary microvascular embolism in CMD rats(P<0.05).WB discovered that STDP pretreatment obviously decreased the expression levels of NF-κB p65,TNF-α,IL-1β,and IL-6 in the myocardium of CMD rats,significantly reduced the expression of Bax,caspase-3 and increased the expression of Bcl-2(P<0.05).Conclusions:The pretreatment with STDP obviously improved coronary microcirculatory function induced by sodium laurate,and its mechanism may be related to its inhibition of inflammatory response,improvement of vascular endothelial function,inhibition of oxidative stress and apoptosis.