| Cerebral Ischemic Stroke is a common modern disease with a high mortality and morbidity rate and a highly complex pathophysiological mechanism following onset. Once the ischemic injury has become irreversible, the disease activates the release of excitatory amino acids, calcium influx, and inflammatory response.Vascular damage leads to increased vascular permeability, allowing leakage of plasma and its water content to accumulate in the extracellular spaces of the brain, and leading to cerebral edema. This is followed by further damage to the brain due to the disruption of the blood-brain barrier (BBB) and cell apoptosis. As a result, more research attention has been directed toward the rehabilitation and treatment of ischemic stroke both at home and abroad. Purpose:This study observes traditional Chinese medicinal compound, Tongluojiunao injection, and its effective components, on a model of Middle Cerebral Artery Occlusionat 24 hours and 72 hours. It observes the rat’s brain function for further insights on the pathology of brain damage, the effects of brain edema and the permeability of BBB, and investigates the diagnosis and treatment efficacy of Tongluojiunao injection.On the other hand, the study also investigates Tongluojiunao injection and prognosis through its constituent Geniposide and Panax notoginsenoside (PNS), and the expression of vascular endothelial growth factor (VEGF) and angiogenin (ANG-1) in ischemic brain tissue. It will also probe treatment of the internal mechanism of cerebral ischemia by Tongluojiunao injection. The study will yield scientific experimental basis for the efficacy and compatibility of the mechanism of Chinese traditional medicine.Methods:1. Healthy male Sprague-Dawley(SD) rats were randomly divided into 5 groups:sham control group (J), model group (M), Geniposide group (Z), PNS group (S), and Tongluojiunao injection group (TLJN).Two days following the administration of Tongluojiunao injection and its component Geniposide and PNS, the Middle Cerebral Artery Occlusion (MCAO) model is prepared. Treatment is administered once again two hours later. Hereafter treatment is given at the same time daily, and data is gathered from the model after 24 hours and again after 72 hours.2. Used neurological function score to observe rats’behavioral change.3. Used HE staining to observe the pathological brain changes of each rat group.4. Determined rat brains’dry weight (DW) to wet weight (WW) ratio to observe water content in the brain.5. Used Evans Blue dye to investigate the effects of drugs on the blood-brain barrier permeability.6. Used Western blot and immunohistochemistry to detect each rat group’s cerebral vascular endothelial growth factor (VEGF) and angiogenin (ANG-1) expression.Results:1. The neurological function score results were as follow:compared with the sham control group, scores for each treatment group were significantly higher (P<0.05), and compared with the model group, scores for each treatment group decreased (P<0.05). At 2-hour and 24 hour points, the Geniposide group, PNS group, and Tongluojiunao Injection group showed a further downward trend, though this was not statistically significant. Only after 72 hours later did the decrease become statistically significant2. Pathomorphology shows, the sham group’s cell structure was intact. The model group showed severe nuclear atrophy, and the intercellular substance showed bubble-like, softened structures. The Geniposide group, PNS group and Tongluojiunao injection group all appeared to show mild ischemic changes, mild cellular swelling, cell atrophy, intercellular substances and morphological changes that were less severe compared with the model group.3. Compared with the sham group, the model group’s brain water content increased (P< 0.05); compared with the model group, water content in the Geniposide group and Tongluojiunao injection group decreased (P<0.05); and compared with the Geniposide group and PNS group, the TLJN injection group showed more significant decrease in water content (P< 0.05).4. Evans Blue results of each group showed that compare with the sham group, the model group’s Evans blue content increased (P< 0.05), and compared with the model group, each treatment group showed decrease (P< 0.05).5. Western blot results showed that compared with the sham group, the model group’s VEGF and ANG-1 expression was high (P< 0.05); compared with the model group, each treatment group showed reduced VEGF and ANG-1 expression (P< 0.05).6. VEGF, ANG-1 immunohistochemical results were consistent with the Western blot.Conclusion:1. Tongluojiunao injection and its components may effectively improve the neurological function in a rat MCAO model of brain damage, improve neurological function, and provide effective protection against pathological changes due to ischemic brain damage.2. Tongluojiunao injection and its components can reduce brain water content in rat MCAO models, reduce BBB permeability, thereby contributing to the protection of BBB. By reducing brain edema, the injection provides an important mechanism in the protection of the brain.3. Tongluojiunao injection and its components can regulate VEGF and ANG-1 expression in the brain tissue after ischemic injury. This may be the molecular target of the injection’s protection of the vascular barrier.4. Geniposide and PNS administration led to improvement in ischemic brain injury in rats; the two dosages differing somewhat in the time intervals between administration and effect. Geniposide showed obvious effects in the early stages of pathological changes in the brain, while the medicinal effets of PNS emerged more in the middle stages of the pathological changes. Tongluojiunao injection is thus superior in its combining the two components, and exhibiting the advantage of compound compatibility. |
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