【作者】 康立源；

【导师】 高秀梅； 张伯礼；

【作者基本信息】 天津中医学院 ， 中医内科学， 2003， 硕士

【摘要】 高血压(EH)是一种世界性的常见疾病，世界各国的患病率高达10％～20％，并可导致脑血管、心脏、肾脏的病变，是多种心脑血管疾病的独立危险因素。心脏是高血压病直接受累的靶器官，主要损害是心肌肥大和心肌间质纤维化。国内外的研究表明，在控制血压的同时，预防和逆转高血压导致的左心室损害是防治高血压病的重要目标。本研究采用自发性高血压大鼠(SHR)模型，观察了单次灌服养血清脑颗粒24小时内，大鼠尾动脉收缩压的变化以及连续给药8周收缩压的变化；并以左心室重(LVW)、左心室重量指数(LVW／BW)反映左心室的肥厚程度，观察其对高血压导致的左心室肥厚(LVH)的影响；测定了左心室心肌中羟脯氨酸含量和Ⅰ型、Ⅲ型胶原比例(Ⅰ／Ⅲ)的变化，观察药物对心肌胶原的影响；采用基因芯片技术，观测了养血清脑颗粒对左心室基因表达谱的影响。试图从以上观测中，研究该药的降压作用；预防和减轻LVH和左心室重建的作用；并从分子水平上探讨中药防治LVH和中药对高血压病靶器官损害保护作用的机制。其结果如下 1．单次灌服养血清脑颗粒，可以使SHR收缩压下降。在给药后约1小时开始显示降压作用，高峰在药后2～4小时之间。2小时后收缩压下降即有统计学意义(p＜0.05)，3小时达到降压高峰约9mmHg。24小时后，收缩压仍比原收缩压低约2mmHg。中、低剂量组降压趋势与高剂量组相同，但强度不及高剂量组。 2．连续给药8周，养血清脑颗粒可以抑制SHR收缩压随月龄的增长而增加的趋势。连续灌药2周后，高剂量组与模型比较，差异即有显著性(p＜0.05)；给药8周后，高剂量组收缩压比模型组低26.1mmHg，其次中剂量组降低16.4mmHg，低剂量组降低10.8mmHg，各剂量组之间有一定的量效关系。 3．养血清脑颗粒各剂量组均有降低LVW的作用，高剂量组与模型组比较具有非常显著差异(p＜0.01)。各剂量组均有降低LVW／BW作用，与模型组比较，中剂量组和高剂量组有统计学意义(p＜0.05)，高剂量组优于卡托普利组。 4．养血清脑颗粒各不同剂量组均能降低左心室心肌胶原蛋白的含量和中文摘要I、m型胶原的比例。其中中剂量组在降低左心室胶原含量方面有统计学意义 (p<0.05)，各组在改善I、111胶原比例方面均有统计学意义(p<0.01)。 5.养血清脑颗粒对心脏基因表达谱有明显影响。初步研究发现，心肌叮BP一2(Latent transforming growth faetor bindi吃proteinZ，LTBp一2)、甘氨酸甲基转移酶(olycine methyltransferase，Gnmt)和p半乳糖昔a 2.6睡液酸转移酶 (Rat beta一galactoside一alpha 2.6一sialyltransferase)的mRNA表达水平明显下调·上调Cn36抗原、心脏脂肪酸结合蛋白(heart fatty aeid binding protein，Fabp3)、丙酞辅酶Ap多肤(Propionyl eoenz帅e A earboxylase，beta pol邓ept，de，peeb)mRNA表达水平。提示养血清脑颗粒可能通过调节多种心脏细胞因子和生物酶的含量及活性，而具有预防和减轻LVH的作用。 结论: 1.单次灌服养血清脑颗粒，可以使SHR收缩压下降。连续给药可以抑制自发性高血压大鼠收缩压随年龄的增加而增加的趋势。 2.养血清脑颗粒有预防和减轻LVH的作用， 3.养血清脑颗粒具有降低心肌间质胶原含量，降低I型、IJI型胶原的比例，有防止和减轻左心室重构的作用。 4.养血清脑颗粒下调心脏LTBP一2的n1RNA表达水平、甘氨酸甲基转移酶、p半乳糖昔Q 2.6唾液酸转移酶。上调CD36抗原、心脏脂肪酸结合蛋白、丙酞辅酶Ap多肤的基因表达水平。更多还原

【Abstract】 Objective: To investigate the antihypertension effect of YXQN on Spontaneous Hypertension Rat (SHR) and search for YXQN’s protective effect on SHR heart. Method: By using SHR, blood pressure measuring machine and several biochemical techniques, we performed our works in the following five items: (1) Measure blood pressure in 4 and 24 hours after the rat was treated with YXQN one time (2) Survey the changes of left ventricular hypertrophy (LVH) caused by hypertension by using left ventricular weight (LVW) and LVW to body weight (BW) ratio (3) Survey the changes of left ventricular myocardial collagen by measuring contain of hydroxyproline (4) Observe type I to type III collagen ratio by using SDS electrophoresis (5) Observe the changes of related genes by DNA microarray. Result:(1) Treating with YXQN one time can reduce the blood pressure of SHR. One hour after YXQN was treated we observed the effect of reducing blood pressure and the peak is after 2 to 4 hours. The blood pressure reduced significantly after 2 hours and the peak is after 3 hours about 9mmHg. The blood pressure is 2mmHg lower than origin after 24hours. The middle and low dose groups also reduce the blood pressure but not yet to the extent of that of high dose group.(2) Different dose groups of YXQN can reduce the blood pressure of SHR. Two weeks after YXQN was treated continuously, the blood pressure is reduced significantly in high dose group compared with model group. YXQN can prevent the development of blood pressure while rats grows.(3) Different dose groups of YXQN can reduce LVW and the effect is significant between high dose group and model group. They also can reduce the ratio of LVW to BW and the effect of middle and high dose groups is significant compared with model group. The effect of high dose group is better than Captopril Tablets group.(4) Different groups can reduce contain of left ventricular myocardial collagenand type I to type III collagen ratio. The effect of middle dose group is significant in reducing contain of collagen. The effect of all groups is significant in reducing ratio of type I to type III collagen.(5) The genes latent transforming growth factor binding protein 2 (LTBP-2), glycine methyltransferase (Gnmt) and rat beta-galactoside-alpha 2.6-sialyltransferase in YXQN group were expressed in lower level than in model group. The genes CD36 antigen, heart fatty acid binding protein (Fabp3) and propionyl Coenzyme A carboxylase beta polypeptide (Pccb) in YXQN group were expressed in higher level than in model group. They may play an important role in preventing LVH Conclusion:(1) Treating with YXQN one time can reduce the blood pressure of SHR.(2) YXQN can prevent the development of blood pressure while rats grows.(3) YXQN can prevent and reduce the development of LVH.(4) YXQN can reduce contain of myocardial collagen and type I to type III collagen ratio, therefore prevent and reduce left ventricular remolding.(5) YXQN can lower the express level of LTBP-2 .更多还原