The Effects Of Ligustrazine On The Expressions Of Cytokines In The Rats Of Actue Pulmonary Thromboembolism And Clinical Cases Analyses Of Pulmonary Embolism

Objective Pulmonary thromboembolism(PTE) is a disorder that thrombi from the vein system or right-sided heart obstruct pulmonary artery or/and its branches. Its primary clinical and pathophysiological characters are obstacles of pulmonary circulation and respiratory function. Its have high morbidity, misdiagnosis and fatality rate and become severer public health issue currently. Further awareness should be enhanced; further measures should be taken to explore PTE's pathogenetic mechanisms and treatment. In view of this, the PTE model of rats was established by intravenous injection of autologous blood clots. We researched rats' changes of general conditions, items of artery blood gas and related cytokines in the blood and pulmonary tissues within a longer time. A certain dose of Ligustrazine was injected. The effects on these items were observed. The roles of these cytokines were further explored. Some certain theoretical bases will be provided for the PTE's clinical treatment.Methods 65 healthy SD rats were dividend into blank group, PTE model group and Ligustrazine treat group randomly. The blank group's rats were no operation at all.Each rats in the PTE model group were operated to form PTE models. Each rats in the Ligustrazine treat group were dealed to operate PTE models firstly, then were treated with daily dose of Ligustrazine 2mg/d by celiac injection. The PTE model group and Ligustrazine treat group were dividend into six points: 1h, 3h, 1d, 3d, 5d and 7d after PTE operation and treatment. Each point has 5 rats. The number of rats in every group were 5, 30, 30 respectively. The PTE model of rats was established by intravenous injection of autologous blood clots. 0.2ml blood was taken from each rat's vein in tail, formed embolus, then was infused into right-sided heart through jugular vein. Weobserved each rat's general conditions at every point, executed them, drew blood from carotid to perform bood gas, extracted blood plasma to mensurate the concentrations of TXB2 and 6-K-PGF1 α by radioimmunoassay. Pulmonary tissues were separated, dyed with routine HE staining to observe pathological changes with light microscope. The expressions of ET-1, COX-2 and CD54 in these tissues were detected by IHC S-P. The expressions of HIF-1 α mRNA and ERK 1/2 in tissues were measured by RT-PCR and Western-blot each.Results (1) General conditions: Rats in the model group were poorer than rats in the blank group, rapider in breath frequency. These cyanosis were obvious. (2) Blood gas: Rats in the model group had a certain acidemia, low PaCO₂ and hypoxemia (P<0.05). These items in the treat group had resumed after 7days therapy of Ligustrazine (P>0.05). (3) Concentrations of TXB₂, 6-K-PGF1 α in plasma and their ratio (T/P): TXB₂ in the model group elevated, higher markly than those in the blank group(P<0.05). These values in the treat group had depressed close to those in the blank group when Ligustrazine treated 5 days (P>0.05). 6-K-PGF1 α in both model group and treat group escalated (P<0.05). T/P in the model group heightened much than those in the blank group ((P<0.05). The treat group's T/P neared the blank group's T/P (P>0.05). (4) Gross anatomy and routine HE staining: The blank group's lungs were flesh, the lungs' structure were complete. There were no thrombi in the pulmonary artery. There were no hemorrhage and edema in the lung tissues. Alveolar septum were normal. In the model group, atelectasis and pieces of hemorrhagic blots were seen. A lots of thrombi in the pulmonary arteries, thicken walls of alveoli and interstitial, infiltrated and exsudated leukocytes were also visible changes in the model group. There were massive edema fluids and erythrocytes. Compared to the model group, the histopathological variations in the treat group were thrombi in the pulmonary arteries disappeared, Inflammatory reactions, haemorrhages and edema lessened obviously, alveolar septum recovered common. (5) The expressions of ET-1, COX-2 and CD54 in the lung tissues: the expressions of these indexes in the model group rose highlier than those in the blank group (P<0.05). In the treat group, the expressions of these indexes were similar to those in the blank group (P>0.05). The expression level on the 7^th day in this group decreasedmuch than levels in the model group (P<0.05). (6) The levels of HIF-1 mRNA in the lung tissues: This item's expression in the blank group was weak. In the model group, at the beginning, the expressions were poor, but after 3 days, it became strong (P<0.05). In the treat group, it was weak too (P>0.05). The expression level on the 7^th day in this group was lower than levels on the 5^th and 7^th day in the model group (P<0.05). (7) The levels of ERK1/2 in the lung tissues: The blank group's ERK1/2 expression was weak. In the model group, it expressed stronglier than that in the blank group (P<0.05). In the treat group, it expressed highlier than that in the blank group also(P<0.05), but it's expression of the 7^th day lessened significantly compare to the expressions in the model group(P<0.05).Conclusion This experiment demonstrated that these cytokines participated in the PTE's physiopathological changes. These were the one of PTE's pathogenesis. Ligustrazine can depress the concentration of vasoconstrictor ET-1 and TXB₂ in the blood of PTE, make vasodilatory mediator rich relatively, then dilate pulmonary vessels. It can degrade the levels of inflammatory cytokines shch as COX-2 and CD54, rectify hypoxemia, lower edema and inflammatory reaction, drop pulmonary artery pressure. So it may have a certain therapeutic effect to PTE patients. Ligustrazine suppressing the expression levels of these cytokines may be the one of its pharmacological mechanisms to therapy pulmonary artery hypertension.