复方降压片的药效学研究
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摘要
复方降压片由钩藤、罗布麻两味药组成。钩藤(Uncaria rhynchopyhlla(Miq)Jackon)属茜草科植物，主要分布于热带地区，其带钩茎枝入药，具有清热平肝、活血通瘀、息风定惊的功效，在我国应用已有悠久的历史。主要用于治疗头晕目眩、惊痫抽搐、全身麻木、高血压等心脑血管和神经系统疾病。罗布麻(Apoacynum venetum L)为夹竹桃科植物，广泛野生于盐碱沙荒地区，其叶入药，具有平肝安神，清热利水之功效，主要用于治疗高血压、哮喘及加强免疫功能。
本实验主要研究由钩藤和罗布麻有效成分组成的复方降压片的降压作用和其对高血压伴随症状的影响。钩藤以80mg/kg经十二指肠一次性给药后，麻醉状态下正常大鼠(ANR)血压在给药45-180min后持续下降，与对照组比较有明显差异。另外，钩藤与罗布麻的有效成分以1：4、1：2、1：1进行配伍组合，即钩藤80mg/kg，罗布麻用药剂量分别为320mg/kg、160mg/kg、80mg/kg。对ANR进行观察，结果表明：各剂量组经十二指肠给药后，均能明显降低正常大鼠的血压，和空白对照组比较有明显意义(P＜0.05-0.001)，因钩藤与罗布麻间比例为1：2的用药量降压效果显著，药量适中，故确定该复方中两味药的比例为1：2。通过小鼠急性毒性试验，确定其灌胃给药LD50为2.924817g/kg，该复方最大给药剂量240mg/kg远低于中毒剂量。
采用两肾一夹方法复制高血压大鼠(2K1C-RHR)模型，大鼠血压在术后三周呈上升趋势，在术后四周血压明显升高并呈稳定状态。RHR在一次性给药8h后血压即明显下降(P＜0.05)，连续给药十天后降到最低(P＜0.05-0.001)，最大降压幅度达22.24％。且通过对该动物模型血浆中血管紧张素(AngⅡ)和心钠素(ANP)含量测定表明，其对ANP含量有增加的趋势，对AngⅡ含量无明显影响。
通过对SHR动物模型降压作用的观察结果表明，240mg/kg剂量组从给药第三天开始，大鼠血压开始明显下降(P＜0.05-0.001)，到给药第16天降到最低(P＜0.001)，降压幅度达18.95％。120mg/kg剂量组，从给药第二天开始降压(P＜0.05-0.01)。60mg/kg剂量组降压效果不明显，仅在给药第三天和第二十天出现显著降压作用(P＜0.05)，呈明显的量效关系。复方降压片使ANP含量显著增高，对AngⅡ影响不明显，对ET含量有降低趋势，但无统计学意义(P＞0.05)。
吉林农业大学硕士学位论文
复方降压片的药效学研究
提示，ANP含量的增加可能是该复方制剂降低血压的机制之一。
通过对豚鼠眩晕模型的治疗作用结果表明，复方降压片可明显改善豚鼠的眩
晕症状，减少豚鼠自耳窝内滴注氛仿后20而n、40而n后的眼球震颤次数和头左
右摇摆次数。
同时本实验通过对血疥动物血液粘度、血沉和红细胞压积测定及体外血检形
成等观察表明，其可明显抑制体外血松的形成。模型组和空白对照组的血栓长度
(em)、湿重(mg)、干重(mg)分别为12.88士1.17、420.75土25.7、108.5士25.7，
而24om乡吸g给药组，分别为10.46士3.25、315.13士74.3(p<0.05)、87士20.87，
120mglkg给药组分别为9.19士21.8(p<0.05)、304.13士74.3(p<0 .05)、79.75
士17.61;60Ing/kg剂量组分别为11.3士2.72、330.25士44.06(p<0.05)、83.88士
12.63(P<0 .05)，可见，给药组和模型组比较有明显差异，提示，复方降压片可
明显抑制大鼠体外血检的形成，使血癣动物全血比粘度、血沉与模型组比明显降
低，但对血浆比粘度及红细胞压积影响不明显。表明其可降低血液粘度，改善血
疥动物血液流变性。提示对于防治心血管疾病有一定作用。
通过对小鼠急性高血脂模型的治疗作用的结果表明，复方降压片622mg般g
可明显降低急性高血脂小鼠的胆固醇水平，和模型组比较有显著意义(P<0.05);
同时，高剂量622m眺g组和中剂量336m眺g组可显著降低高血脂小鼠的甘油
三醋水平，和模型组比较，有显著意义(P<0.05)。结果提示，其可以从降低胆
固醇、甘油三醋的角度，防止动肪硬化的形成，有助于抑制高血压的形成，对高
血压患者的恢复具有重要意义。
Abstract Fu Fang Jiang Ya Plan is comprised of the effective ingredient of Uncaria rhynchopyhlly and Apoacynum venetun L. Uncaria rhynchopyhlla is Rubiaceae plant and distributed mainly tropical regions, which has long applied history in china and is used usually to treating cardiovascular and nervous system diseases, such as light-headedness,convulsion,numbness,hypertension, etc. Apoacynum venetum L. is Apocynaceae plant. Its root has diuretic effect; the leaf can decrease blood pressure and enhance immunologic function. Furthermore, Its decoction has the action of sedation and analgesia.
In our experiment, we studied the effects of Fu Fang Jiang Ya Pian on blood pressure and the symptom relevant to hypertension. Rhychoplline (Rhy) is a major effective ingredient extracted from Uncaria rhynchopyhlly ,80mg/kg of which can decrease obviously ANR's blood pressure by the means of injecting through duodenum . Furthermore, the ratio of Rhy to the effective ingredient of Apocynum 1:4 1: 2 1: 1 is given separately through duodenum to the ANR, each dose of them can decrease the ANR's blood pressure, however, the ratio of Rhy to Apocynum 1:2 is better and more stable than the other doses. Therefore, in Fu Fang Jiang Ya Pian, we decide that the optimal dose of po. is 240mg/kg, namely Rhy is 80mg/kg, the effective ingredient of Apocynum is 160mg/kg.
We duplicated the model of 2K1C-RHR, the results indicate that after operation the rats' blood pressure are elevated obviously than before operation, the range is approximately 30mmhg .It means the model of hypertension is successful. 240mg/kg 120mg/kg 60mg/kg were given po. for 10 days, RHR' blood pressure can be obviously decreased (P<0.05-0.001). At the end of the continuous given 10th day, the blood pressure decrease to the minimum, the maximal range of decreasing blood pressure is 22.24%. Meanwhile, we assay the content of Angll and ANP, the results indicate that Fu Fang Jiang Ya Pian can increase the content of ANP, but the effect
isn't obvious; the changing of ANP is little.
In SHR, Fu Fang Jiang Ya Pian(24(K 120 60mg/kg) were given po. for 20 days, the increasing of blood pressure of SHR was inhibited obviously from the third day (P<0.05). At the end of the 20th day, SHR' blood pressure decreased to the minimum, the maximal range wasl8.95%. Moreover, AngII ANP ET were measured. The result showed the content of ANP between test and control groups was very obvious, this may be one of the mechanisms of decreasing blood pressure. However, AngII ET have no change compare with control group.
In guinea pig's vertigo model, Fu Fang Jiang Ya Pian can relief the dazzle symptom of guinea pig, lessen significantly eyeball tremor and head shaking numbers caused by dripping chloroform from guinea pigs' ears.
In the meanwhile, we observed the effect of Fu Fang Jiang Ya Pian on rats' blood rheology .The results suggested that the tested medicine can decrease obviously the whole viscosity blood sedimentation. The difference between the test and the control groups was very notable. Moreover, the tested medicine can suppressed significantly the formation of the ex vivo thrombosis. The results showed Fu Fang Jiang Ya Pian might improve the rheology of blood stasis animals, which is good to preventing cardiovascular diseases.
In mice' hyperlipemia model, Fu Fang Jiang Ya Pian was given po. for five days ,at the end of the fifth day, the total cholesterol, triglyceride were measured, the results showed that the difference between test and control groups was obvious, which indicated Fu Fang Jiang Ya Pian may decrease blood fat level of animals, and prevent indirectly the enhancement of hypertension.
To sum up, Fu Fang Jiang Ya Pian can effectively decrease animal blood pressure and relief the symptom relevant to hypertension. Moreover, Its toxicity is little. Therefore, Fu Fang Jiang Ya Pian has a wide progress promising.
本实验主要研究由钩藤和罗布麻有效成分组成的复方降压片的降压作用和其对高血压伴随症状的影响。钩藤以80mg/kg经十二指肠一次性给药后，麻醉状态下正常大鼠(ANR)血压在给药45-180min后持续下降，与对照组比较有明显差异。另外，钩藤与罗布麻的有效成分以1：4、1：2、1：1进行配伍组合，即钩藤80mg/kg，罗布麻用药剂量分别为320mg/kg、160mg/kg、80mg/kg。对ANR进行观察，结果表明：各剂量组经十二指肠给药后，均能明显降低正常大鼠的血压，和空白对照组比较有明显意义(P＜0.05-0.001)，因钩藤与罗布麻间比例为1：2的用药量降压效果显著，药量适中，故确定该复方中两味药的比例为1：2。通过小鼠急性毒性试验，确定其灌胃给药LD50为2.924817g/kg，该复方最大给药剂量240mg/kg远低于中毒剂量。
采用两肾一夹方法复制高血压大鼠(2K1C-RHR)模型，大鼠血压在术后三周呈上升趋势，在术后四周血压明显升高并呈稳定状态。RHR在一次性给药8h后血压即明显下降(P＜0.05)，连续给药十天后降到最低(P＜0.05-0.001)，最大降压幅度达22.24％。且通过对该动物模型血浆中血管紧张素(AngⅡ)和心钠素(ANP)含量测定表明，其对ANP含量有增加的趋势，对AngⅡ含量无明显影响。
通过对SHR动物模型降压作用的观察结果表明，240mg/kg剂量组从给药第三天开始，大鼠血压开始明显下降(P＜0.05-0.001)，到给药第16天降到最低(P＜0.001)，降压幅度达18.95％。120mg/kg剂量组，从给药第二天开始降压(P＜0.05-0.01)。60mg/kg剂量组降压效果不明显，仅在给药第三天和第二十天出现显著降压作用(P＜0.05)，呈明显的量效关系。复方降压片使ANP含量显著增高，对AngⅡ影响不明显，对ET含量有降低趋势，但无统计学意义(P＞0.05)。
吉林农业大学硕士学位论文
复方降压片的药效学研究
提示，ANP含量的增加可能是该复方制剂降低血压的机制之一。
通过对豚鼠眩晕模型的治疗作用结果表明，复方降压片可明显改善豚鼠的眩
晕症状，减少豚鼠自耳窝内滴注氛仿后20而n、40而n后的眼球震颤次数和头左
右摇摆次数。
同时本实验通过对血疥动物血液粘度、血沉和红细胞压积测定及体外血检形
成等观察表明，其可明显抑制体外血松的形成。模型组和空白对照组的血栓长度
(em)、湿重(mg)、干重(mg)分别为12.88士1.17、420.75土25.7、108.5士25.7，
而24om乡吸g给药组，分别为10.46士3.25、315.13士74.3(p<0.05)、87士20.87，
120mglkg给药组分别为9.19士21.8(p<0.05)、304.13士74.3(p<0 .05)、79.75
士17.61;60Ing/kg剂量组分别为11.3士2.72、330.25士44.06(p<0.05)、83.88士
12.63(P<0 .05)，可见，给药组和模型组比较有明显差异，提示，复方降压片可
明显抑制大鼠体外血检的形成，使血癣动物全血比粘度、血沉与模型组比明显降
低，但对血浆比粘度及红细胞压积影响不明显。表明其可降低血液粘度，改善血
疥动物血液流变性。提示对于防治心血管疾病有一定作用。
通过对小鼠急性高血脂模型的治疗作用的结果表明，复方降压片622mg般g
可明显降低急性高血脂小鼠的胆固醇水平，和模型组比较有显著意义(P<0.05);
同时，高剂量622m眺g组和中剂量336m眺g组可显著降低高血脂小鼠的甘油
三醋水平，和模型组比较，有显著意义(P<0.05)。结果提示，其可以从降低胆
固醇、甘油三醋的角度，防止动肪硬化的形成，有助于抑制高血压的形成，对高
血压患者的恢复具有重要意义。
Abstract Fu Fang Jiang Ya Plan is comprised of the effective ingredient of Uncaria rhynchopyhlly and Apoacynum venetun L. Uncaria rhynchopyhlla is Rubiaceae plant and distributed mainly tropical regions, which has long applied history in china and is used usually to treating cardiovascular and nervous system diseases, such as light-headedness,convulsion,numbness,hypertension, etc. Apoacynum venetum L. is Apocynaceae plant. Its root has diuretic effect; the leaf can decrease blood pressure and enhance immunologic function. Furthermore, Its decoction has the action of sedation and analgesia.
In our experiment, we studied the effects of Fu Fang Jiang Ya Pian on blood pressure and the symptom relevant to hypertension. Rhychoplline (Rhy) is a major effective ingredient extracted from Uncaria rhynchopyhlly ,80mg/kg of which can decrease obviously ANR's blood pressure by the means of injecting through duodenum . Furthermore, the ratio of Rhy to the effective ingredient of Apocynum 1:4 1: 2 1: 1 is given separately through duodenum to the ANR, each dose of them can decrease the ANR's blood pressure, however, the ratio of Rhy to Apocynum 1:2 is better and more stable than the other doses. Therefore, in Fu Fang Jiang Ya Pian, we decide that the optimal dose of po. is 240mg/kg, namely Rhy is 80mg/kg, the effective ingredient of Apocynum is 160mg/kg.
We duplicated the model of 2K1C-RHR, the results indicate that after operation the rats' blood pressure are elevated obviously than before operation, the range is approximately 30mmhg .It means the model of hypertension is successful. 240mg/kg 120mg/kg 60mg/kg were given po. for 10 days, RHR' blood pressure can be obviously decreased (P<0.05-0.001). At the end of the continuous given 10th day, the blood pressure decrease to the minimum, the maximal range of decreasing blood pressure is 22.24%. Meanwhile, we assay the content of Angll and ANP, the results indicate that Fu Fang Jiang Ya Pian can increase the content of ANP, but the effect
isn't obvious; the changing of ANP is little.
In SHR, Fu Fang Jiang Ya Pian(24(K 120 60mg/kg) were given po. for 20 days, the increasing of blood pressure of SHR was inhibited obviously from the third day (P<0.05). At the end of the 20th day, SHR' blood pressure decreased to the minimum, the maximal range wasl8.95%. Moreover, AngII ANP ET were measured. The result showed the content of ANP between test and control groups was very obvious, this may be one of the mechanisms of decreasing blood pressure. However, AngII ET have no change compare with control group.
In guinea pig's vertigo model, Fu Fang Jiang Ya Pian can relief the dazzle symptom of guinea pig, lessen significantly eyeball tremor and head shaking numbers caused by dripping chloroform from guinea pigs' ears.
In the meanwhile, we observed the effect of Fu Fang Jiang Ya Pian on rats' blood rheology .The results suggested that the tested medicine can decrease obviously the whole viscosity blood sedimentation. The difference between the test and the control groups was very notable. Moreover, the tested medicine can suppressed significantly the formation of the ex vivo thrombosis. The results showed Fu Fang Jiang Ya Pian might improve the rheology of blood stasis animals, which is good to preventing cardiovascular diseases.
In mice' hyperlipemia model, Fu Fang Jiang Ya Pian was given po. for five days ,at the end of the fifth day, the total cholesterol, triglyceride were measured, the results showed that the difference between test and control groups was obvious, which indicated Fu Fang Jiang Ya Pian may decrease blood fat level of animals, and prevent indirectly the enhancement of hypertension.
To sum up, Fu Fang Jiang Ya Pian can effectively decrease animal blood pressure and relief the symptom relevant to hypertension. Moreover, Its toxicity is little. Therefore, Fu Fang Jiang Ya Pian has a wide progress promising.
引文
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