| Background Ischemic cerebrovascular disease is a type of cerebrovascular disease,which refers to cerebrovascular disease or systemic disease of brain tissue ischemia and hypoxia caused by a series of circulation obstacle,and nerve function defect disorder.A survey made by Health ministry in 2012 revealed that our country population of more than 10 million stroke over the age of 40,including ischemic stroke accounted for 80%,has had a serious social and economic burden.Therefore,making enough researches on the pathophysiological mechanisms of the elderly ICVD patients and searching after positive and effective therapy pathway is valuable.Acute ischemic pathological changes of brain tissue can be divided into core necrotic area and around the half dark zone surrounding the core of ischemia.Irreversible damage to nerve cells in central necrotic area,and ischemia half dark stripe in a state of low oxygen and low perfusion.At present,one of the main therapies is to recover blood flaw of the cerebral ischemic penumbra so as to rescue reversible ischemic cerebral tissue.In the process of this therapy,however,it is easy to form a further exacerbation of cerebral ischemic injury called cerebral ischemia-reperfusion injury(CIRI).Recently,researches had found that new vessels exist around the ischemic reperfusion areas.The formation and extension of the new vessels can increase blood and oxygen supply of the ischemic areas so as to help relieve I/R injury and improve dysneuria.But in the process of angiogenesis is relatively weak,it offers good prospects for the development of the TAG.The further researcesh have demonstrated that activating some signal paths can participate in adjusting the process of angiogenesis,while the AC-c AMP-PKA signal path play an important role in the formation of the new vessels among these signal paths.Some factors which are phosphorylated by the AC-c AMP-PKA signal path(such as CREB?p-CREB,etc.)participate in regulating the formation of functional vascular with the cooperation of other signal paths and then have key impact on I/R injury repair.This paper has two parts including experiment study and clinical efficacy evaluation.The former discusses the characteristics of the capillaries generation of those aged rats who suffered from brain I/R and analyzes the influence of the Chinese herbal compound Naomaitong on the capillaries generation and possible internal mechanism after I/R by contrasting and observing dysneuria degree,brain tissue ultrastructure and positive expression change of the CREB,p-CREB in the perimeter area of the cerebral cortex ischemia with the introduction of the rat focal middle cerebral artery occlusion model.The latter evaluates curative effect of the Chinese herbal compound Naomaitong on cerebral ischemic injury by contrasting evaluation results of the NIHSS scale,traditional Chinese medicine symptom classification scale in the selected elderly patients who suffered from cerebral infarction in different times.Objective 1.In this experiment we will choose the experimental carrier for male SD rats.T he experiment will go through comparison of each simulation experimental rats(including young model group,aging model group,nimodipine group and Naomaitong group).observing every group rats after cerebral ischemia(I)3h reperfusion(I / R)24h,3d,6d,12 d nerve dysfunction and cerebrovascular ultrastructural changes;2.Through observation of the above four groups of rats I3 h,I / R24 h,I / R 3d,I / R 6d,I / R 12 d cerebral cortex CREB?p-CREB expression,judgment the aged rats CREB?p-CREB expression rule.At the same time observe the role of Naomaitong;3.In clinical research,By contrasting grades of the NIHSS scale and traditional Chinese medicine symptom classification scale of those selected elderly cerebral infarction patients who were admitted to hospital on the first day,fourteenth and twenty-eighth day of treatment to evaluate improvement conditions of the Naomaitong on dysneuria of the elderly cerebral infarction patient.Methods 1.Contrasting the degree of the neurological function injury and the changes of the brain tissue ultrastructure among the young rat model group,the aged rat model group,the Nimodipine rat group and Naomaitong rat group under the situation of experiencing cerebral I 3h and I/R 24 h,3d,6d,12 d with introduction of the improved longa8 division method,immunohistochemical staining and electron microscope observation technology;2.Contrasting the expression changes of CREB and p-CREB in the perimeter of thecerebral cortex ischemia among the young rat model group,the aged rat model group,the Nimodipine rat group and the Naomaitong rat group under the situation of experiencing cerebral I 3h and I/R 24 h,3d,6d,12 d with introduction of immunohistochemical staining and light microscope observation technology.3.Contrasting changes of dysneuria degree of those elderly cerebral infarction patients who were admitted to hospital on the first day,fourteenth and twenty-eighth day of treatment with adoption of methods including the NIHSS scale and traditional Chinese medicine symptom classification scale.Results 1.The changes of the brain tissue ultrastructure and the dysneuria after suffering from cerebral I/R of the aged rat and impact of the Naomaitong on the changes.The dysneuria grades of each timing for the aged rat model group are showing a rising trend with time going on,declining gradually after reaching a peak in I/R 24 h,and the dysneuria grades of I/R 6d and I/R 12 d decline sharply(P<0.05,P<0.01);In contrast with the young rat model group at the same timing,the dysneuria grades of the aged rat model group in I/R 24 h rise(P<0.05).In contrast with the aged rat model group at the same timing,the dysneuria grades of the Nimodipine rat group in I/R 24 h reduce(P<0.05)while the dysneuria grades of the Naomaitong rat group reduces in I/R 24 h and 3d(P<0.05).In contrast with the Nimodipine rat group,the dysneuria grade of the Naomaitong rat group has no significant difference.The dysneuria grades of the Naomaitong rat group is showing a rising trend with time going on,declining gradually after reaching a peak in I/R 24 h and reaching the minimum in I/R 12d(P<0.01).2.The time-histories changes of the CREB expression after suffering from cerebral I/R of the aged rat and impact of the Naomaitong on the expression.A little CREB expression can be observed from the aged rat sham-operation group.The expression is gradually rising with time going on,declining after reaching a peak in I/R 24 h and the CREB positive expression of the aged rat model group in I/R 6d,12 d decrease sharply,reaching the minimum in I/R 12d(P<0.05,P<0.01).In contrast with the young rat sham-operation group,the CREB positive expression of the aged rat sham-operation group rises(P<0.01);In contrast with the young rat model group at the same timing,the CREB positive expression of the aged rat model group in I/R 24 h rises(P<0.05)while the CREB positive expression of the aged rat model group in I/R 3d,6d all reduces(P<0.05,P<0.01).In contrast with the aged rat model group at the same timing,the CREB positive expression of the Nimodipine rat group in I/R 3d,6d,12 d all rises(P<0.01).The CREB positive expression of the Naomaitong rat group in I/R 24 h,3d,6d,12 d all rises(P<0.05,P<0.01).In contrast with the nimodipine rat group at the same timing,the CREB positive expression of the Naomaitong rat group in I/R 3d reduces(P<0.01)while the CREB positive expression of the Naomaitong rat group in I/R 6d,12 d all rises(P<0.05,P<0.01).The CREB expression of the Naomaitong rat group is gradually rising with time going on,declining after reaching a peak in I/R 6d and reaching a minimum in I/R 12 d,but the CREB expression of the Naomaitong rat group is still higher than that of the I 3h(P<0.05,P<0.01).3.The time-histories changes of the p-CREB expression after suffering from cerebral I/R with the aged rat and impact of the Naomaitong on the expression.A little p-CREB expression can be observed from the aged rat sham-operation group.The expression is gradually rising as time goes on,declining after reaching a peak in I/R 24 h,reaching the minimum in I/R 12d(P<0.05,P<0.01).In contrast with the young rat sham-operation group,the p-CREB expression of the aged rat sham-operation rises(P<0.01);In contrast with the young rat model group at the same timing,the p-CREB positive expression of the aged rat model group in I/R 3h?24h rises(P<0.01)while the p-CREB positive expression of the aged rat model group in I/R 3d,6d reduces(P<0.05,P<0.01).In contrast with the aged rat model group at the same timing,the p-CREB positive expression of the Nimodipine rat group in I/R 3d,6d,12 d all rises(P<0.01)while the p-CREB positive expression of the Naomaitong rat group in I/R 6d,12 d all rises(P<0.01).In contrast with the Nimodipine rat group at the same timing,the p-CREB positive expression of the Naomaitong rat group in I/R 24 h reduces(P<0.05)while the p-CREB positive expression of the Naomaitong rat group in I/R 12 d rises(P<0.01).The p-CREB expression of the Naomaitong rat group is gradually rising with time going on,slowly declining after reaching a peak in I/R 6d(P<0.05,P<0.01).4.The impact of the Naomaitong on the grades changes of the NIHSS scale and traditional Chinese medicine symptom classification scale for the elderly cerebral infarction patients.The effect of group difference,time difference and the interaction of grouping and time on grades of NIHSS scale and traditional Chinese medicine symptom classification scale of the selected elderly cerebral infarction patients have statistical significance(P<0.05).The grades of NIHSS scale and traditional Chinese medicine symptom classification scale of the Naomaitong and the control group on the fourteenth and twenty-eighth day of treatment are lower than those in the day of admission(P<0.05).The grades of traditional Chinese medicine symptom classification scale of theNaomaitong group on the fourteenth and twenty-eighth day of treatment are lower than those of the control groups(P<0.05).The grades of NHISS scale of the Naomaitong group on the twenty-eighth day of treatment are lower than those of the control group(P<0.05).Conclusion 1.Against older group of rats with the youth group rats nerve dysfunction rating,and microstructure change situation analysis of the radiographic findings,the old mice are more prone to cerebral ischemic injury after change,which have less fresh capillaries and slow recovery.At the same time,damage is heavier than youth rats;2.The expression of aging rats CREB?p-CREB peak earlier than young rats,but maintain shorter,reduce rapidly.Two treatment group expression level of CREB?p-CREB were improved compared with model group.Contrast the use of Nimodipine and Naomaitong treatment effect,therapeutic effect of group Naomaitong is better;3.These results demonstrate that Naomaitong can improve the neurologic function injury of the elderly patients with acute cerebral infraction. |
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