本文選題：腦出血急性期 + 中醫(yī)分階段治療��； 參考：《成都中醫(yī)藥大學》2016年博士論文

【摘要】：第一部分：臨床觀察目的：通過臨床觀察腦出血急性期應用中醫(yī)分階段治療方案對患者相關指標的影響,研究中醫(yī)分階段治療方案對腦出血急性期治療的臨床療效,從而制定符合臨床實際、規(guī)范化且行之有效、易于推廣應用的腦出血急性期的臨床治療方案,以期提高該病的臨床療效。方法：采用隨機平行對照的臨床試驗方法,納入腦出血急性期患者,共60例,隨機分為觀察組和對照組,每組各30例,其中對照組采用西醫(yī)常規(guī)治療,包括穩(wěn)定生命體征、控制血壓、血糖、營養(yǎng)神經(jīng)、改善腦代謝等；觀察組在此基礎上采用中醫(yī)分階段治療方案,針對急性期不同階段分別給予中藥湯劑辨證施治,中成藥、針灸理療等方法進行治療,兩組均于治療前及治療后14d對患者的臨床療效及中醫(yī)癥狀分級量表評分、NIHSS評分、Rankin評分、Barthel指數(shù)評分講行檢測,并于治療前、治療后7d及14天對患者顱內(nèi)血腫的變化情況以及安全性指標,包括血常規(guī)、肝腎功、凝血等進行檢測,從而比較兩組的臨床療效和對上述指標的影響情況,分析并評價兩組的有效性和安全性。結(jié)果：1、中醫(yī)分階段治療方案組(觀察組)患者的中醫(yī)癥狀分級量表評分、NIHSS評分、Rankin評分、Barthel指數(shù)評分、顱內(nèi)血腫體積改善情況均明顯優(yōu)于單純西醫(yī)治療組(對照組),P0.05；觀察組的中醫(yī)證候療效、西醫(yī)臨床療效、顱內(nèi)血腫療效均明顯高于對照組,P0.05；2、兩種治療方案對患者的生命體征、肝腎功、血常規(guī)、凝血等指標均未造成不良影響,具有較好的安全性。結(jié)論：對腦出血急性期患者采用中醫(yī)分階段治療方案較單純西醫(yī)治療能夠更加有效的使患者神經(jīng)功能得到改善,從而提高患者治愈率,并改善生活質(zhì)量,安全有效,值得推廣。第二部分：動物實驗目的：探討蛭龍活血通瘀膠囊對腦出血大鼠腦水腫、血腦屏障功能的影響,并研究該藥腦保護的作用機制,為蛭龍活血通瘀膠囊在腦出血急性期的臨床運用提供科學的實驗依據(jù)。方法：取255只雄性、健康的SD大鼠,采用隨機分組法分為假手術組、模型組、蛭龍活血通瘀膠囊高、中、低劑量組,各組又根據(jù)指標檢測的時間不同劃分為12h、48h、72h三個亞組,采用自體血注入法制備腦出血大鼠模型,各藥物組于術后分別給予蛭龍活血通瘀膠囊灌胃,每日量分別為0.3g/kg、0.6g/kg和1.2g/kg,而模型組和假手術組則灌胃與藥物組同等體積的生理鹽水,3ml／次,給藥次數(shù)及時間同藥物組。各組進行相應干預后,在各規(guī)定的時間點對大鼠神經(jīng)行為學評分(NSS)進行測定,取出腦組織,檢測大鼠腦含水量及腦系數(shù),HE染色對大鼠腦出血血腫周圍組織行病理學觀察,采用伊文思藍法檢測血腦屏障的通透性,電子顯微鏡觀察血腦屏障的超微結(jié)構(gòu),Western-blot法檢測與腦水腫相關的蛋白AQP-4、MMP-9及TIMP-1的表達,PT-PCR法檢測AQP-4、MMP-9及TIMP-1 mRNA表達。結(jié)果：1、腦出血模型大鼠在術后12h可見腦組織水腫,48h及72h腦水腫程度逐漸加重,神經(jīng)功能缺損情況逐漸明顯,NSS評分隨之升高,腦含水量及腦系數(shù)也逐漸升高,HE染色見腦組織明顯水腫,間質(zhì)疏松,血腫周圍結(jié)構(gòu)紊亂。蛭龍活血通瘀膠囊低、中、高劑量組在術后12h、48h及72h,大鼠腦水腫情況均較模型組有所改善,神經(jīng)功能評分較之下降,腦含水量及腦系數(shù)也較之下降(P0.01),HE染色可見腦組織血腫周圍水腫均有不同程度的改善,各藥物組之間比較以高劑量組改善最為明顯。2、腦出血模型大鼠在術后12h血腦屏障的通透性即可發(fā)現(xiàn)有明顯改變,腦組織EB含量明顯升高,術后48h時升高最為明顯,72h時稍有下降。電鏡超微結(jié)構(gòu)顯示術后48h,整個血管腔形態(tài)不規(guī)則,基膜厚薄不均,毛細血管周圍水腫明顯,組織稀疏,電子密度降低,內(nèi)皮局部膨出,部分與基膜剝離,血腦屏障結(jié)構(gòu)發(fā)生破壞。蛭龍活血通瘀膠囊低、中、高劑量組在術后12h、48h及72h,大鼠血腦屏障通透性較模型組均具有不同程度的改善(P0.01),腦組織EB含量較之有所下降,電鏡超微結(jié)構(gòu)觀察發(fā)現(xiàn)血管周圍水腫程度較為輕微,血腦屏障的結(jié)構(gòu)得到明顯改善,以高劑量組改善最為明顯。3、腦出血模型大鼠在術后12h、48h及72h腦組織中AQP-4、MMP-9、TIMP-1蛋白及基因的表達均有明顯上升,其中,AQP-4蛋白及基因表達呈進行性升高,在72h時升高最為明顯,MMP-9、TIMP-1蛋白及基因表達也有明顯升高,在48h時上升明顯并達到高峰,在72h時略有下降。而蛭龍活血通瘀膠囊低、中、高劑量組在術后12h、48h及72h時大鼠腦組織AQP-4、MMP-9蛋白及基因的相對表達量均有不同程度的下降,TIMP-1蛋白及基因的相對表達量有所升高,與模型組比較,差異均具有顯著性(P0.01),不同劑量組間比較,高劑量組最為明顯(P0.01)。結(jié)論：1、蛭龍活血通瘀膠囊能夠明顯改善腦出血大鼠神經(jīng)功能缺損癥狀,使神經(jīng)功能缺損評分有所減輕,并降低腦出血大鼠腦含水量及腦系數(shù),從而使腦組織水腫程度得到明顯改善。2、蛭龍活血通瘀膠囊能夠明顯改善腦出血大鼠血腦屏障的通透性,使腦組織EB含量有所減輕,保護血腦屏障的組織結(jié)構(gòu)避免血腦屏障受到破壞,從而減輕腦組織的水腫程度。3、蛭龍活血通瘀膠囊能夠明顯降低腦出血大鼠腦組織AQP-4、MMP-9蛋白及基因的表達,同時升高TIMP-1蛋白及基因的表達,從而改善血腫周圍腦組織水腫。4、蛭龍活血通瘀膠囊上述藥理作用存在一定的量效關系,以高劑量組作用最為明顯。
[Abstract]:The first part: clinical observation: through the clinical observation of the acute phase of cerebral hemorrhage, the clinical effect of the phased therapy of TCM on the related indexes of the patients was studied, and the clinical effect of the phased therapy of TCM on the treatment of acute cerebral hemorrhage was studied so as to formulate the cerebral hemorrhage which was in accordance with the clinical practice, standardized and effective, and easy to be popularized and applied. In order to improve the clinical efficacy of the acute phase in order to improve the clinical efficacy of the disease. Methods: a randomized parallel controlled clinical trial was adopted to include 60 cases of acute cerebral hemorrhage. A total of 30 patients in each group were randomly divided into the observation group and the control group. The control group was treated with routine western medicine, including the stable vital signs, the control of blood pressure, blood sugar, and the camp. On the basis of this, the observation group was treated with Chinese traditional Chinese medicine decoction, Chinese traditional medicine, acupuncture and moxibustion and other methods for treatment. The two groups were treated before and after the treatment of the two groups, the clinical curative effect of the patients and the scale of TCM symptoms rating scale, NIHSS evaluation. Score, Rankin score, Barthel index score, and before treatment, after 7d and 14 days after treatment, the changes in the patient's intracranial hematoma and safety indexes, including blood routine, liver and kidney work, coagulation and so on, were detected to compare the clinical efficacy of the two groups and the effects on the above indications, and to analyze and evaluate the effectiveness and safety of the two groups. Results: 1, the TCM symptom classification scale score, NIHSS score, Rankin score, Barthel index score, the improvement of intracranial hematoma volume were obviously better than that of the simple western medicine treatment group (control group), P0.05, the curative effect of TCM syndrome in the observation group, the clinical effect of Western medicine and the curative effect of intracranial hematoma in the observation group. Obviously higher than the control group, P0.05; 2, two kinds of treatment schemes have no adverse effects on the patient's vital signs, liver and kidney work, blood routine, coagulation and so on. Conclusion: the treatment of acute cerebral hemorrhage in patients with acute stage of cerebral hemorrhage can be more effective than pure Western Medicine to make the patient's nerve function more effective. To improve the cure rate and improve the quality of life, and improve the quality of life, it is safe and effective, and it is worth popularizing. The second part: the objective of animal experiment: To explore the effect of hirudon Huoxue Tongyu Capsule on brain edema and blood brain barrier function of rats with cerebral hemorrhage, and to study the mechanism of the protective action of the drug for the acute stage of cerebral hemorrhage in the leeudon Huoxue Tongyu capsule. Methods: 255 male and healthy SD rats were divided into sham operation group, model group, hirudon Huoxue Tongyu capsule high, middle and low dose group, and three subgroups of 48h and 72h were divided into three subgroups according to the index detection time. The model of autologous blood injection was used to prepare the rat model of cerebral hemorrhage. After the operation, each drug group was given the gavage of hirudon Huoxue Tongyu capsule, respectively, 0.3g/kg, 0.6g/kg and 1.2g/kg, respectively, and the model group and the sham operation group were treated with the same volume of saline, 3ml / times, the times and time of the administration. The behavior score (NSS) was measured, the brain tissue was taken out, the brain water content and the brain coefficient were detected. HE staining was used to observe the tissue around the hematoma and hematoma in rats. The permeability of the blood brain barrier was detected by Evans blue, the ultrastructure of the blood brain barrier was observed by electron microscope, and the protein A related to brain edema was detected by the Western-blot method. The expression of QP-4, MMP-9 and TIMP-1 and the expression of AQP-4, MMP-9 and TIMP-1 mRNA were detected by PT-PCR. Results: 1, the brain edema was observed at 12h in the rat model of cerebral hemorrhage, the degree of 48h and 72h cerebral edema gradually increased, the nerve function defect was gradually obvious, the NSS score increased, the brain water content and brain coefficient increased gradually, and the brain tissue was stained to see the brain tissue. Edema, interstitial loosening, structure disorder around hematoma, leech Huoxue Tongyu capsule low, middle, high dose group after 12h, 48h and 72h, brain edema in rats were improved compared with the model group, neural function score was lower, brain water content and brain coefficient decreased (P0.01), HE staining showed that edema around brain hematoma around hematoma can be found to be different The improvement of the degree was the most obvious.2 in the high dose group. The permeability of the 12h blood barrier in the cerebral hemorrhage model rats could be found obviously, the EB content of the brain tissue increased obviously, the 48h increased most obviously after the operation, and the 72h decreased slightly. The ultrastructure of the electric microscope showed 48h after operation, and the whole vascular cavity form was not. Rules, the thickness of the basement membrane was uneven, the edema around capillaries was obvious, the tissue was sparse, the electron density was reduced, the endothelia was partially expanded, the blood brain barrier structure was partially destroyed by the basement membrane and the blood brain barrier structure was destroyed. The permeability of the blood brain barrier in the high dose group was 12h, 48h and 72h in the high dose group, and the permeability of blood brain barrier in the rat was improved to a different degree (P 0.01) the content of EB in brain tissue was lower than that of it. Ultrastructural observation of electron microscope showed that the degree of edema around blood vessels was slight, the structure of blood brain barrier was obviously improved, and the most obvious.3 was improved in high dose group. The expression of AQP-4, MMP-9, TIMP-1 protein and gene expression in 12h, 48h and 72h brain tissues of cerebral hemorrhage model rats were obvious. In addition, the expression of AQP-4 protein and gene showed progressive increase, the most obvious increase at 72h, MMP-9, TIMP-1 protein and gene expression was also significantly increased, at the time of 48h increased and reached the peak, a slight decrease in 72h, while the leech dragon Huoxue Tongyu capsule was low, medium and high dose group in 12h, 48h and 72h rat brain AQP-4, MMP-9 protein in postoperative 12h, 48h and 72h. The relative expression of the gene and the relative expression of TIMP-1 protein and gene increased. Compared with the model group, the difference was significant (P0.01). The high dose group was the most obvious (P0.01). Conclusion: 1, hirudon live blood Tongyu capsule can obviously improve the neural function deficiency in rats with cerebral hemorrhage. The loss of symptoms, reduce the score of neural function defect, reduce the brain water content and brain coefficient of cerebral hemorrhage rats, so that the degree of brain edema is obviously improved by.2. The permeability of blood brain barrier in rats with cerebral hemorrhage can be improved obviously, the content of EB in brain tissue is reduced and the tissue structure of the blood brain barrier can be protected. To avoid the damage of blood brain barrier and reduce the edema degree of brain tissue.3, hirudon Huoxue Tongyu capsule can obviously reduce the expression of AQP-4, MMP-9 protein and gene in brain tissue of rats with cerebral hemorrhage, and increase the expression of TIMP-1 protein and gene, so as to improve the pharmacological action of the edema.4 of the brain group around the hematoma and the capsule of hirudon Huoxue Tongyu capsule. There is a certain dose effect relationship. The effect of high dose group is the most obvious.
【學位授予單位】：成都中醫(yī)藥大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R277.7
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本文編號：2097337