| BackgroundAs one of the common diseases clinically,ischemic cerebrovascular disease(ICVD)produces serious threats to human health and life quality with its relatively higher morbidity,case fatality and disability rates.For many reasons including suffering from more underlying diseases,living with some long-standing and interactional dangerous factors,the elderly patients are inclined to be the main group of ICVD.Therefore,making enough researches on the pathophysiological mechanisms of the elderly ICVD patients and searching after positive and effective therapy pathway will significantly reduce the social and medical pressure brought by the disease.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 ischemic/reperfusion(I/R)injury.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.The further researches have demonstrated that activating some signal paths can participate in adjusting the generation of new vessels,while the Notch signal path play an important role in the formation of the new vessels among these signal paths.Some factors(such as Jaggedl,Sox17,etc.)which are in the upstream or downstream of the Notch signal path 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 cerebral I/R and analyzes the influence and the possible internal mechanism of the Chinese herbal compound Naomaitong on the capillaries generation after I/R by contrasting and observing dysneuria degree,microvessel density and positive expression change of the Jaggedl,Sox17 at different time-points in the perimeter area of the cerebral cortex ischemia with the introduction of the MCAO model rats.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 and activity of daily living scale in the selected elderly patients who suffered from cerebral infarction in different timesObjective1 By contrasting dysneuria grades and microvessel density among the young rat model group,the aged rat model group,Nimodipine rat group and Naomaitong rat group under the situation of experiencing cerebral ischemia(I)3h?ischemic reperfusion(I/R)24h,3d,6d,12d to make analysis on the characteristics of brain tissue angiogenesis and the protective effect of the Naomaitong on it;2 By contrasting the positive expression change of Jagged 1 and Sox 17 in the perimeter area of the cerebral cortex ischemia among the young rat model group,the aged rat model group,Nimodipine rat group and Naomaitong rat group under the situation of experiencing cerebral I 3h?I/R 24h,3d,6d,12d to analyze expressive laws of the Jaggedl and Sox17 and the influence of the Naomaitong on it;3 By contrasting grades of the NIHSS scale,traditional Chinese medicine symptom classification scale and activity of daily living scale of those selected elderly cerebral infarction patients who were divided into the Naomaitong group and control group 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.Methods1 Contrasting the changes of dysneuria grades and microvessel density 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 24h,3d,6d,12d with introduction of the improved longa 8 division method,immunohistochemical staining and light microscope observation technology;2 Contrasting the expression changes of Jaggedl and Sox17 in the perimeter of the cerebral 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 24h,3d,6d,12d with introduction of immunohistochemical staining and light microscope observation-technology;3 Contrasting changes of dysneuria degree of those elderly cerebral infarction patients who were divided into the Naomaitong group and control group on the first day,fourteenth and twenty-eighth day of treatment with adoption of methods including the NIHSS scale,traditional Chinese medicine symptom classification scale and activity of daily living scale.Results1 The changes of the microvessel density and the dysneuria after suffering from cerebral I/R of the aged rat and impact of the Naomaitong on the changes.1.1 The dysneuria The dysneuria grades of each timing for the aged rat model group are showing a rising trend with I/R time prolonging,declining gradually after reaching a peak in I/R 24h,and the dysneuria grades of I/R 6d and I/R 12d 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 24h 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 24h reduce(P<0.05)while the dysneuria grades of the Naomaitong rat group reduce in I/R 24h 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 I/R time going on,declining gradually after reaching a peak in I/R 24h and reaching the minimum in I/R 12d.1.2 The microvessel density A small number of new capillaries can be observed in the aged rat sham-operation group.The MVD of aged rat model group is rising with I/R time prolonging,gradually declining after reaching a peak in I3h.The MVD of the aged rat model group in I/R 6d,12d which show a significant drop are all lower than that of the aged rat sham-operation and the time in I3h and I/R 24h(P<0.05,P<0.01).In contrast with the young mouse sham-operation group,the MVD of the aged rat sham-operation group rises(P<0.05);In contrast with the young rat model at the same timing,the MVD of the aged rat model group in I/R 24h,3d,6d,12d all reduces(P<0.05,P<0.01).In contrast with the aged rat model group at the same timing,the MVD of the Nimodipine rat group in I/R 24h,3d,6d,12d all rises(P<0.05)while the MVD of the Naomaitong rat group in I3h,I/R24h,3d,6d,12d all rises(P<0.01);In contrast with the Nimodipine rat group at the same timing,the MVD of the Naomaitong rat group in I3h,I/R12d all rises(P<0.01).The MVD of the Naomaitong rat group is gradually rising with I/R time going on,declining after reaching a peak in I/R 24h,the MVD of the Naomaitong rat group in I/R 6d,12d which show a sharply decrease are all lower than that of the time in I/R 24h(P<0.05,P<0.01).2 The time-histories changes of the Jaggedl positive expression after suffering from cerebral I/R of the aged rat and impact of the Naomaitong on the expression.A little Jaggedl positive expression can be observed from the aged rat sham-operation group.The expression is gradually rising with I/R time going on,declining after reaching a peak in I/R 24h and the Jagged1 positive expression of the aged rat model group in I/R 6d,12d decrease sharply(P<0.05,P<0.01).In contrast with the young rat sham-operation group,the Jaggedl 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 Jaggedl positive expression of the aged rat model group in I/R 24h rises(P<0.05)while the Jaggedl positive expression of the aged rat model group in I/R 3d,6d all reduces(P<0.01).In contrast with the aged rat model group at the same timing,the Jaggedl positive expression of the Nimodipine rat group in I/R 3d,6d,12d all rises(P<0.01).The Jagged1 positive expression of the Naomaitong rat group at the each timing all rises(P<0.05,P<0.01).In contrast with the nimodipine rat group at the same timing,the Jaggedl positive expression of the Naomaitong rat group in I/R 3d reduces(P<0.01)while the Jaggedl positive expression of the Naomaitong rat group in I/R 6d,12d all rises(P<0.05).The Jaggedl positive expression of the Naomaitong rat group is gradually rising with I/R time going on,declining after reaching a peak in I/R 6d and reaching a minimum in I/R 12d which is still higher than that of the I 3h(P<0.05,P<0.01).3 The time-histories changes of the Sox17 positive expression after suffering from cerebral I/R with the aged rat and impact of the Naomaitong on the expression.A little Sox 17 positive expression can be observed from the aged rat sham-operation group.The expression is gradually rising as I/R time goes on,declining after reaching a peak in I/R 24h,and the Sox 17 positive expression of the aged rat model group in I/R 3d,6d,12d decrease sharply(P<0.01).In contrast with the young rat sham-operation group,the Sox 17 positive expression of the aged rat sham-operation rises(P<0.01);In contrast with the young rat model group at the same timing,the Sox 17 positive expression of the aged rat model group in I/R 24h rises(P<0.01)while the Soxl7 positive expression of the aged rat model group in I/R 3d,6d,12d reduces(P<0.05,P<0.01).In contrast with the aged rat model group at the same timing,the Sox17 positive expression of the Nimodipine rat group in I/R 3d,6d,12d all rises(P<0.01)while the Sox 17 positive expression of the Naomaitong rat group in I/R 6d,12d all rises(P<0.01).In contrast with the Nimodipine rat group at the same timing,the Sox17 positive expression of the Naomaitong group in each time shows no significant difference.The Sox17 positive expression of the Naomaitong rat group is gradually rising with I/R time going on,slowly declining after reaching a peak in I/R 6d,and the Sox17 positive expression of I/R 3d and 6d are higher than that of I 3h(P<0.05,P<0.01).4 The impact of the Naomaitong on the grades changes of the NIHSS scale,traditional Chinese medicine symptom classification scale and activity of daily living 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 of the selected elderly cerebral infarction patients have statistical significance(P<0.05).The grades of NIHSS scale of the Naomaitong group on the fourteenth and twenty-eighth day of treatment are lower than those of the control groups(P<0.05).The grades of NIHSS scale of the Naomaitong and Nimodipine group on the fourteenth and twenty-eighth day of treatment are lower than those in the day of admission(P<0.05).The effect of group difference,time difference and the interaction of grouping and time on grades of traditional Chinese medicine symptom classification scale of the selected elderly cerebral infarction patients have statistical significance(P<0.05).The grades of traditional Chinese medicine symptom classification scale of the Naomaitong group on the fourteenth and twenty-eighth day of treatment are lower than those of the control groups(P<0.05).The grades of traditional Chinese medicine symptom classification scale of the Naomaitong and Nimodipine group on the fourteenth and twenty-eighth day of treatment are lower than those in the day of admission(P<0.05).The effect of group difference,time difference and the interaction of grouping and time on grades of activity of daily living scale of the selected elderly cerebral infarction patients have statistical significance(P<0.05).The grades of activity of daily living scale of the Naomaitong group on the fourteenth and twenty-eighth day of treatment are higher than those of the control groups(P<0.05).The grades of activity of daily living scale of the Naomaitong and Nimodipine group on the fourteenth and twenty-eighth day of treatment are higher than those in the day of admission(P<0.05).Conclusion1 With the time of the cerebral I/R prolonging,the rat neurologic function injury will be worse,but can recover by itself.The neurologic function injury of the aged rat is worse and slower repair than that of the young rat,and one of the reasons may be the less angiogenesis of the aged rat suffered from the cerebral I/R.The fact that degree of the neurologic function injury of the Nimodipine group and the Naomaitong group is lighter than that of the aged rat model group has something to do with the fact that the Nimodipine and the Naomaitong can promote the angiogenesis in aged rat after suffering from the cerebral I/R;2 A little Jagged 1 and Sox 17 positive expression can be observed after the rat suffered from the cerebral ischemia and the expression is gradually rising as the time of the cerebral I/R goes on.The characteristic that the Jagged 1 and Sox17 positive expression of the aged rat reaches a peak earlier than that of the young rat does,but keeps short maintenance and reduces rapidly could be one of the reasons that the neurologic function injury of the aged rat at the same timing is worse.The Jaggedl and Sox 17 positive expression of the Naomaitong group show higher and the peaks come later but keep longer maintenance than the aged rat group.This fact demonstrates that the mechanism that Naomaitong can promote angiogenesis of the aged rat after suffering from the cerebral I/R may be related to its promotion in the Jagged1 and Sox 17 positive expression on the ischemic penumbra;3 Naomaitong can significantly reduces the the grades of the NIHSS scale and the traditional Chinese medicine symptom classification scale of elderly patients with acute cerebral infraction,and the medicine also can increases the grades of the activity of daily living scale of the patients.These results demonstrate that Naomaitong can improve the neurologic function injury of the elderly patients with cerebral infraction. |
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