| Objective:Based on spontaneously hypertensive rats,the carotid artery sodium laurate injection method was combined with long-term irritation to induce the formation of an animal model of yin deficiency and yang hyperactivity and blood stasis in hypertension-lacuna infarction comorbidity,and evaluate animal models from multiple perspectives of behavior,morphology,function,biochemistry and molecular.On this basis,the pharmacodynamic effects of compound Qishao antihypertensive tablets on yin deficiency and yang hyperactivity and blood stasis in hypertension-lacuna infarction comorbidity were explored,in order to provide more experimental basis for the clinical application of compound Qishao antihypertensive tablets.Methods:1.Establishment and evaluation of animal model of yin deficiency and yang hyperactivity and blood stasis in hypertension-lacuna infarction comorbidity: 20 spontaneously hypertensive rats were randomly divided into a model group and a sham operation group,with 10 rats in each group,and another 10 Wistar Kyoto rats were used as a control group.Rats in the model group were injected with the internal carotid artery sodium laurate injection method.The sham operation group was treated with normal saline in the internal carotid artery,and the control group did not do any treatment.The skin color of the rats,the changes in the drinking water diet,the condition of the urine and the irritability and irritability were observed daily.Conduct behavioral tests on the 3rd and 7th day after modeling,and on the 7th day after modeling,the serum and brain tissues of rats were taken for blood lipid,endothelin-1,plasminogen activator inhibitor-1,optical microscopy and transmission electron microscopy.2.Intervention of compound Qishao antihypertensive tablets on yin deficiency and yang hyperactivity and blood stasis in hypertension-lacuna infarction comorbidity: 40 spontaneously hypertensive rats were randomly divided into model group,western medicine group(nifedipine tablets + citicoline sodium tablets),Chinese medicine group(compound Qishao antihypertensive tablets)and sham operation group,10 in each group,and another 10 Wistar Kyoto rats were usedas a control group.The rats in the model group,the western medicine group and the traditional Chinese medicine group were modeled by the injection of the internal carotid artery sodium laurate.The sham operation group was treated with the internal carotid artery injected with physiological saline,and the control group did not do any treatment.The model group,the sham operation group and the control group were administered with pure water.The western medicine group was given nifedipine tablets + citicoline sodium tablets,and the Chinese medicine group was given the compound Qishao antihypertensive tablets.The rat tail artery systolic pressure was measured once every 7 days during the experiment.After 14 days of intervention,rat serum and brain tissue were taken for serum lipid,high-sensitivity C-reactive protein,homocysteine,endothelin-1 and plasminogen activator inhibitor-1 levels,as well as endothelin-1,nitric oxide,thromboxane and prostacyclin-related protein expression levels in brain tissue.Results:1.Establishment and evaluation of animal model of yin deficiency and yang hyperactivity and blood stasis in hypertension-lacuna infarction comorbidity:(1)After modeling with the internal carotid artery sodium laurate injection method,rats in the model group developed nervousness and irritability.At the same time,there was a dull yellow color,a lot of hair loss,a small amount of secretions in the corner of the eye,a small amount of dark yellow urine,a dry texture of the stool,and a small particle size.(2)Compared with the control group,the blood pressure of the model group and the sham operation group was significantly increased,and it showed a significant upward trend after modeling.(3)In the model group,there were obvious neurological deficits in the posture reflex test,the limb asymmetry application test and the corner test.However,there was no neurological deficit in the control group and the sham operation group.(4)Compared with the control group,serum total cholesterol,triglyceride,and low-density lipoprotein cholesterol levels in the sham-operated group and the model group were significantly increased,but there was no significant difference between the groups at the high-density lipoprotein cholesterol level.(5)The levels of serum endothelin-1 and plasminogen activator inhibitor-1 in the model group were higher than those in the control group,and there was no significant differencebetween the sham operation group and the sham operation group.(6)HE staining: Control group and sham operation group: The number of neurons is large,the cell morphology is intact,the nucleus is large and round,and the intact nucleolus is visible in the nucleus.Model group: Deep perforating arterial stenosis,thrombosis in some lumens,occlusion of the lumen,inflammatory cell infiltration around the blood vessels;nucleus condensing of some neurons around the blood vessels,eosinophilic staining,nucleolus Disappeared,the cell structure is unclear,and there is inflammatory cell infiltration around it.(7)Transmission electron microscopy results: In the model group,the deep perforating artery was damaged in the brain,the cell membrane was broken,and the vascular edema of the peripheral blood vessels was observed.The vascular cavity was deformed by compression and the interstitial tissue gap was widened.Partial deep perforating artery showed separation of vascular endothelium from vascular basement membrane.In some areas,astrocytes are swollen,accompanied by edema of the foot,chromatin accumulation in the nucleus,edge collection,and some mitochondria appear vacuolization.Occasionally,necrotic neurons can be seen,and the cell morphology and structure are unclear.The chromatin in the nucleus aggregates into a lump,and the nucleolus disappears,showing mitochondrial swelling and cavitation.There was no obvious damage to the middle cerebral artery,and the structure of the intima of the blood vessel was intact.It was found that the continuous tight connection and the vascular peripheral matrix showed no obvious edema.2.Intervention of compound Qishao antihypertensive tablets on yin deficiency and yang hyperactivity and blood stasis in hypertension-lacuna infarction comorbidity:(1)After 7 days of feeding and gavage,the systolic blood pressure of the tail artery of the sham operation group and the model group showed a significant upward trend,while the systolic blood pressure of the tail artery of the western medicine group and the Chinese medicine group was significantly lower than that before the administration,and the decrease was roughly equivalent.After 14 days of feeding and gavage treatment,the blood pressure of the rats in each group showed no significant change compared with the previous measurement.This suggests that both Western medicine intervention and Chinese medicine intervention can obtain a good and stable antihypertensive effect,and the antihypertensive effect is roughly equivalent.(2)After 14 days of corresponding drug intervention,the levels of serum total cholesterol,triglyceride,and low-density lipoprotein cholesterol in the western medicine group and the Chinese medicine group were lower than those in the model group,and the reduction in the Chinese medicine group was larger than that in the western medicine group.According to the statistical results,there was no significant difference between the rats in the group and the control group at the serum HDL-C level.(3)After 14 days of corresponding drug intervention,the expression of endothelial nitric oxide synthase and prostacyclin synthase CYP8A1 in the brain tissue of the western medicine group and the Chinese medicine group were higher than those in the model group,and the increase was roughly equivalent.The brain tissue thrombin synthase CYP5A1 and endothelin-1in the western medicine group and the Chinese medicine group were lower than the model group in terms of the number of positive targets and the positive target optical density,and the decrease was roughly equivalent.(4)After 14 days of corresponding drug intervention,the levels of serum high-sensitivity C-reactive protein,endothelin-1 and homocysteine in the western medicine group and the Chinese medicine group were lower than those in the model group,and the decline was similar in the two groups;while in the serum plasminogen activator inhibitor-At the 1 level,the Chinese medicine group was lower than the model group and the western medicine group.Conclusion:1.The animal model constructed by spontaneously hypertensive rats combined with internal carotid artery sodium laurate injection method not only meets the clinical pathogenesis and pathological changes of hypertension-lacuna infarction comorbidity,but also meets the conditions of TCM syndromes of yin deficiency and yang hyperactivity and blood stasis syndrome.It is proved that the method successfully prepared the animal model of yin deficiency and yang hyperactivity and blood stasis in hypertension-lacuna infarction comorbidity.2.Compound Qishao antihypertensive tablets can protect blood vessels of small and small arteries and arteries by lowering blood pressure,regulating lipid metabolism disorder,inhibiting the expression of vasoconstrictor in the brain,and promoting the expression of vasodilators in brain tissue.Endothelial function,inhibition of excessive activation of the coagulation system,and reduction of local inflammatory responses to the target organs.Compound Qishao antihypertensive tablets can protect the vascular endothelium function of brain micro-arteries,inhibit the excessive activation of the coagulation system and reduce the local inflammatory reaction of the blood vessels to protect the target organs by lowering blood pressure,regulating lipid metabolism disorder,inhibiting the expression of vasoconstrictor in the brain,and promoting the expression of vasodilators in brain tissue. |
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