| Objective:(1)Establishment of a rat model of acute pulmonary embolism.(2)Observation on the therapeutic effect of salvianolate on acute pulmonary embolism.(3)Observing the expression of inflammation-related factors IL-1?,IL-6,IL-10,IL-13 and TNF-? by Salvia miltiorrhiza polyphenolate can protect lung tissue,improve prognosis and explore its possible mechanism.Methods:(1)35 Sprague-Dawley rats were randomly divided into sham operation group(SHAM group),pulmonary embolism model group(MODEL group),low molecular weight heparin positive control group(LMWH group),and salvia miltiorrhiza polyphenolate low dose group(LOW group),and Danshen polyphenolate high dose group(HIGH group),7 in each group.Rats were cut from the tail to take blood,and autologous thromboembolism was prepared.The autologous thromboembolism was obtained from the jugular vein to make a rat model of acute pulmonary embolism.Rats in the SHAM group were injected with the same amount of normal saline.LMWH group was injected intraperitoneally with LMWH(Kesel,0.01ml/kg)immediately after model establishment.Immediately after modeling in LOW group and HIGH group,Danshen polyphenolate(10mg/kg,30mg/kg)Q12h was injected intraperitoneally for5 times.The SHAM group and the MODEL group were intraperitoneally injected with the same amount of normal saline,and the time was the same as the previous group.All rats were sacrificed on day 4 in each group.(2)ELISA for serum D-dimer(D-Dimer),brain natriuretic peptide(BNP),and troponin(c Tn T).(3)EILSA detection of serum IL-6,IL-10,TNF-? concentration.(4)Detection of m RNA expression of IL-1?,IL-6,IL-10,IL-13 and TNF-? in lung tissue by Real-time RT-PCR.(5)Western Blot detection of ERK protein expression in lung tissue.(6)Pathological section HE staining was used to observe the lung tissue of each group.(7)Differences in construction were compared by t test or one-way ANOVA.P<0.05 was considered significant.Results:(1)All the 28 rats except the Sham group were injected with emboli,2 patients died in the LMWH group 2 hours after operation,and 1 died in the LOW group 36 hours after surgery.The rest did not die.A total of 25 rat models of acute pulmonary embolism were made,and the success rate of modeling was 89.3%.All rats had shortness of breath,cyanosis,and heart rate after injection of embolism.(2)The serum D-Dimer concentration in the model group was significantly higher than that in the sham-operated group(P<0.05).The serum D-Dimer of the Danshen polyphenolate low-dose group and the Danshen polyphenolate high-dose group decreased compared with the model group(P<0.05).(3)The serum IL-6 concentration in the model group was significantly higher than that in the sham-operated group(P<0.05).The serum IL-6 concentration in the high-dose salvianolate group was significantly lower than that in the model group(P<0.05).(4)The expressions of IL-?,TNF-?,IL-6,IL-10 and IL-13 m RNA in the lung tissue of the model group were significantly higher than those in the sham operation group(P<0.05).The low dose of Danshen polyphenolate group and Danshendu The expressions of TNF-?,IL-6,IL-10 and IL-13 m RNA in lung tissue of rats with high dose of phenolate were significantly lower than those in the model group(P<0.05).(5)The phosphorylation level of ERK1/2 protein in the model group was higher than that in the sham operation group.The phosphorylation level of ERK1/2 protein in the low dose group of Danshen polyphenolate group and the high dose group of Salvianolate was lower than that in the model group.(6)Pathological sections of the lungs of the model group showed thrombus in the vascular lumen,irregular alveolar size,thickened interstitial lung and a large number of inflammatory cell infiltration.Salvianolate polyphenolate reduced the pathological changes of rat lung tissue,and the small thrombus in the lung was also significantly reduced.(7)There was no significant difference between the experimental results of the low dose group of salvianolate and the high dose group of salvianolate.Conclution:(1)The ideal rat model of acute pulmonary embolism can be prepared by autologous thromboembolism.(2)Salvianolate can reduce the pathological damage of rats with acute pulmonary embolism,reduce the small thrombus in the lung,reduce the concentration of D-Dimer in peripheral serum,and have a therapeutic effect on acute pulmonary embolism.(3)One of the mechanisms of action of salvianolate is to accelerate the thrombus lysis by inhibiting the expression of inflammatory factors in lung tissue,and to protect the lung tissue after acute pulmonary embolism and improve the prognosis.(4)One of the mechanisms by which salvia polyphenolate inhibits inflammation may be through inhibition of MEK/ERK signaling pathway expression. |
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