破血化瘀，填精补髓法对实验性脑出血大鼠血肿周围组织损伤修复的研究
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摘要
目的：探讨破血化瘀，填精补髓法对实验性脑出血大鼠血肿周围组织损伤修复的机制，为临床治疗提供可靠的实验学依据，完善髓虚毒损脑病发病病机关键学说，丰富脑髓理论。
方法：本实验用WISTAR大鼠复制脑出血大鼠模型，设计实验观察应用破血化瘀，填精补髓法方剂在改善脑出血大鼠神经功能缺损、血肿吸收、脑含水量等整体动物行为学指标的作用；设计实验观察神经营养因子及血管内皮生长因子蛋白表达情况，选择表达明显的蛋白进一步设计实验观察相应受体的蛋白的表达情况及该信号转导通路的mRNA的表达情况。
结果：
（1）与模型组相比，阳性药和受试药各组大鼠在给药1天和3天后能明显改善大鼠神经系统体征，降低神经功能缺损评分；到第7天基本恢复正常。
（2）与模型组相比，阳性药和受试药各组大鼠在给药3天和7天后能明显降低脑出血面积比，统计学有意义（P<0.01）。
（3）与模型组相比，阳性药和受试药各组大鼠在给药3天和7天后脑含水量明显降低，统计学有意义（P<0.05,P<0.01）。
（4）在给药第3天，与模型组比较受试药高剂量和中剂量明显增加了损伤脑区BDNF阳性细胞数量（P<0.01，P<0.05）。在给药第7天，与模型组比较，阳性药组、受试药各剂量组均明显增加了损伤脑区BDNF阳性细胞数量（P<0.001，P<0.01，P<0.05）。在给药第14天，与假手术组比较，受试药高剂量和中剂量明显增加了损伤脑区BDNF阳性细胞数量（P<0.01，P<0.05）。
（5）在给药第1、3、7天，与模型组比较，阳性药组及受试药低剂量组对损伤时脑区NGF阳性细胞数量并没有明显的影响（P>0.05，P>0.05，P>0.05）。在给药第14天，与模型组比较，阳性药组、受试药高剂量和中剂量明显增加了损伤脑区NGF阳性细胞数量（P<0.01，P<0.01）。
（6）在给药第1、3天，与模型组比较，受试药高剂量和中剂量明显增加了损伤脑区VEGF阳性细胞数量（P<0.01，P<0.05）；在给药第7天，与模型组比较，阳性药组，受试药高剂量、中剂量和低剂量均明显增加了损伤脑区VEGF阳性细胞数量（P<0.01，P<0.01，P<0.05）。在给药第14天，与模型组比较，受试药高剂量和中剂量明显增加了损伤脑区VEGF阳性细胞数量（P<0.01，P<0.01）。
（7）在给药第1天，与模型组比较，受试药高剂量组明显增加了损伤脑区TrkB阳性细胞数量（P<0.05）。在给药第3天，与模型组比较，受试药高剂量和中剂量明显增加了损伤脑区TrkB阳性细胞数量（P<0.05，P<0.05）。在给药第7、14天，与模型组比较，阳性药醒脑健神胶囊对损伤时脑区TrkB阳性细胞数量有提升，但无统计学意义（P>0.05）。受试药高剂量和中剂量均明显增加了损伤脑区TRKB阳性细胞数量（P<0.01，P<0.05）。
（8）与假手术组大鼠比较，在给药7天后阳性药组与模型组大鼠比较BDNFmRNA表达量略升高，但没有显著性差异（P>0.05）；受试药中剂量组和高级量组与模型组大鼠比较BDNFmRNA表达量明显增加（P<0.01,P<0.01）。而受试药低剂量组与模型组大鼠比较BDNFmRNA表达量也有显著性差异（P<0.05）。
（9）在给药7天后阳性药组与模型组大鼠比较TrkB mRNA表达量略升高，但没有显著性差异（P>0.05）；受试药中剂量组和高级量组与模型组大鼠比较TrkB mRNA表达量明显增加（P<0.05,P<0.05）。而受试药低剂量组与模型组大鼠比较TrkB mRNA表达量没有显著性差异（P>0.05）。
结论：通过实验证明了应用破血化瘀，填精补髓法方剂能明显改善脑出血大鼠神经功能缺损、促进血肿吸收、降低脑含水量；从蛋白水平证明其作用机制可能为调高脑出血灶血肿周围损伤组织中BDNF及受体TrkB、NGF、VEGF蛋白表达有关；从基因水平证明其作用机制可能为调高脑出血灶血肿周围损伤组织中BDNFmRNA及受体TrkBmRNA表达有关。
Objective: The experiment is to investigate The Effect of Decoction of Poxue Huayu and TianjingBusui to the Perihematomal Tissue in Experimental ICH Rats. To provide reliable experimental evidencefor clinical treatment, and to complete the pathogenesis theory of Suixu Dusun encephalopathy andencephala theory.
Methods: The experiment use WISTAR rat to copy the model rats of cerebral hemorrhage. It isdesigned to observe the effect of the behavioristic index that how the Poxue Huayu and Tianjing Busuimethod could improve the neurological deficit, hematoma’s assimilate and and the brain water content.There is also a experiment which is designed to observe the protein expression of neurotrophic factor andvascular endothelial growth factor. And we also need to choose a protein which’s expression is obvious tomake an advanced experiment to observe the certain receptor’s protein’s expression condition and mRNA’sexpression of the signal transduction pathways.
Results:
(1)Compared with the model group, the masculine drug and the investigational drug groups’ rats’neurological signs are improved after one and three days’ administration, and the neurological deficit scoreare declined.
(2)Compared with the model group, the masculine drug and the investigational drug groups’ rats’cerebral hemorrhage area ratio are declined after one and three days’ administration, which has thestatistical significance(P<0.01).
(3)Compared with the model group, the masculine drug and the investigational drug groups’ rats’ brainwater content are declined markedly, which has the statistical significance(P<0.01).
(4)At the third day of administration, compared with the model group, the high-dose and medium-doseinvestigational drug groups’ damaged brain area’s BDNF masculine cells’ quantity are clearlyincreased(P<0.01,P<0.05). At the seventh day after administration, compared with the model group, themasculine drug and all doses’ groups’ damaged brain area’s BDNF masculine cells quantity are clearlyincreased(P<0.001,P<0.01,P<0.05). At the fourteenth day after administration, compared with the shamoperation group, the high and medium-dose of the investigational drug group’s damaged brain area’s BDNFmasculine cells’ quantity are clearly increased(P<0.01,P<0.05).
(5)At the first, the third and the seventh day of the administration, compared with the model group, themasculine drug and low-dose investigational drug groups’ damaged brain area’s NGF masculine cellsquantity are not significantly affected(P>0.05,P>0.05,P>0.05). At the fourteenth day, compared with themodel group, the masculine drug, high and medium-dose group’s damaged brain area’s NGF masculinecells’ quantity are clearly increased(P<0.01,P<0.01).
(6)At the first and third day, compared with the model group, the high and medium-doseinvestigational drug groups’ damaged brain area’s VEGF masculine cells quantity are clearlyincreased(P<0.01,P<0.05); and at the seventh day, compared with the model group the masculine drug, high,medium and low-dose groups’ damaged brain area’s VEGF masculine cells’ quantity are clearlyincreased(P<0.01,P<0.01,P<0.05). At the fourteenth day after administration, compared with the modelgroup, the high and medium-dose groups’ damaged brain area’s VEGF masculine cells’ quantity areclearly increased(P<0.01,P<0.01).
(7)At the first day of administration, compared with the model group, he high-dose investigationaldrug groups’ damaged brain area’s TrkB masculine cells’ quantity are clearly increased(P<0.05). At the third day of administration, compared with the model group, high and medium-dose groups’ damaged brainarea’s TrkB masculine cells’ quantity are clearly increased(P<0.05,P<0.05).At the seventh and fourteenthday, compared with the model group the masculine drug XINGNAOJIAN capsule group’s damaged brainarea’s TrkB masculine cells’ quantity are increased but it is not statistically significant(P>0.05). Theinvestigational drug and medium-dose group all increase the damaged brain area’s TrkB masculine cells’quantity(P<0.01,P<0.05).
(8)Compared with the sham operation group, after seven days’ administration, compared with modelgroup the expression of the masculine drug groups’ BDNFmRNA is increased which is not statisticallysignificant; the high and medium-dose investigational drug groups’ BDNFmRNA expression is clearlyincreased(P<0.01, P<0.01). And the difference of BDNFmRNA expression between low-dose and modelgroups is significant(P<0.05).
(9)After seven days’ administration, the expression of TrkB mRNA is slightly increased between themasculine drug group and model group which don’t show the statistical differences(P>0.05); the high andmedium-dose groups’ expression of TrkB mRNA is increased significantly compared with the modelgroup(P<0.05,P<0.05). But the difference of the expression between low-dose and model group is notsignificant(P>0.05).
Conclusion: The experiment has proved that the intracerebral hemorrhage rats’ neurological deficit,absorption of hematoma and decline of brain water content has been evidently improved by the PoxueHuayu and Tianjing Busui prescription. And it has been proved from the molecular level that themechanism might be that the BDNF, NGF, VEGF’s protein expression surround the hematoma of thecerebral hemorrhage have been increased. The Genetic level mechanism might be that the BDNFmRNAreceptor’s expression which surround the surrounding tissue of the hematoma of the cerebral hemorrhagehas been increased.
方法：本实验用WISTAR大鼠复制脑出血大鼠模型，设计实验观察应用破血化瘀，填精补髓法方剂在改善脑出血大鼠神经功能缺损、血肿吸收、脑含水量等整体动物行为学指标的作用；设计实验观察神经营养因子及血管内皮生长因子蛋白表达情况，选择表达明显的蛋白进一步设计实验观察相应受体的蛋白的表达情况及该信号转导通路的mRNA的表达情况。
结果：
（1）与模型组相比，阳性药和受试药各组大鼠在给药1天和3天后能明显改善大鼠神经系统体征，降低神经功能缺损评分；到第7天基本恢复正常。
（2）与模型组相比，阳性药和受试药各组大鼠在给药3天和7天后能明显降低脑出血面积比，统计学有意义（P<0.01）。
（3）与模型组相比，阳性药和受试药各组大鼠在给药3天和7天后脑含水量明显降低，统计学有意义（P<0.05,P<0.01）。
（4）在给药第3天，与模型组比较受试药高剂量和中剂量明显增加了损伤脑区BDNF阳性细胞数量（P<0.01，P<0.05）。在给药第7天，与模型组比较，阳性药组、受试药各剂量组均明显增加了损伤脑区BDNF阳性细胞数量（P<0.001，P<0.01，P<0.05）。在给药第14天，与假手术组比较，受试药高剂量和中剂量明显增加了损伤脑区BDNF阳性细胞数量（P<0.01，P<0.05）。
（5）在给药第1、3、7天，与模型组比较，阳性药组及受试药低剂量组对损伤时脑区NGF阳性细胞数量并没有明显的影响（P>0.05，P>0.05，P>0.05）。在给药第14天，与模型组比较，阳性药组、受试药高剂量和中剂量明显增加了损伤脑区NGF阳性细胞数量（P<0.01，P<0.01）。
（6）在给药第1、3天，与模型组比较，受试药高剂量和中剂量明显增加了损伤脑区VEGF阳性细胞数量（P<0.01，P<0.05）；在给药第7天，与模型组比较，阳性药组，受试药高剂量、中剂量和低剂量均明显增加了损伤脑区VEGF阳性细胞数量（P<0.01，P<0.01，P<0.05）。在给药第14天，与模型组比较，受试药高剂量和中剂量明显增加了损伤脑区VEGF阳性细胞数量（P<0.01，P<0.01）。
（7）在给药第1天，与模型组比较，受试药高剂量组明显增加了损伤脑区TrkB阳性细胞数量（P<0.05）。在给药第3天，与模型组比较，受试药高剂量和中剂量明显增加了损伤脑区TrkB阳性细胞数量（P<0.05，P<0.05）。在给药第7、14天，与模型组比较，阳性药醒脑健神胶囊对损伤时脑区TrkB阳性细胞数量有提升，但无统计学意义（P>0.05）。受试药高剂量和中剂量均明显增加了损伤脑区TRKB阳性细胞数量（P<0.01，P<0.05）。
（8）与假手术组大鼠比较，在给药7天后阳性药组与模型组大鼠比较BDNFmRNA表达量略升高，但没有显著性差异（P>0.05）；受试药中剂量组和高级量组与模型组大鼠比较BDNFmRNA表达量明显增加（P<0.01,P<0.01）。而受试药低剂量组与模型组大鼠比较BDNFmRNA表达量也有显著性差异（P<0.05）。
（9）在给药7天后阳性药组与模型组大鼠比较TrkB mRNA表达量略升高，但没有显著性差异（P>0.05）；受试药中剂量组和高级量组与模型组大鼠比较TrkB mRNA表达量明显增加（P<0.05,P<0.05）。而受试药低剂量组与模型组大鼠比较TrkB mRNA表达量没有显著性差异（P>0.05）。
结论：通过实验证明了应用破血化瘀，填精补髓法方剂能明显改善脑出血大鼠神经功能缺损、促进血肿吸收、降低脑含水量；从蛋白水平证明其作用机制可能为调高脑出血灶血肿周围损伤组织中BDNF及受体TrkB、NGF、VEGF蛋白表达有关；从基因水平证明其作用机制可能为调高脑出血灶血肿周围损伤组织中BDNFmRNA及受体TrkBmRNA表达有关。
Objective: The experiment is to investigate The Effect of Decoction of Poxue Huayu and TianjingBusui to the Perihematomal Tissue in Experimental ICH Rats. To provide reliable experimental evidencefor clinical treatment, and to complete the pathogenesis theory of Suixu Dusun encephalopathy andencephala theory.
Methods: The experiment use WISTAR rat to copy the model rats of cerebral hemorrhage. It isdesigned to observe the effect of the behavioristic index that how the Poxue Huayu and Tianjing Busuimethod could improve the neurological deficit, hematoma’s assimilate and and the brain water content.There is also a experiment which is designed to observe the protein expression of neurotrophic factor andvascular endothelial growth factor. And we also need to choose a protein which’s expression is obvious tomake an advanced experiment to observe the certain receptor’s protein’s expression condition and mRNA’sexpression of the signal transduction pathways.
Results:
(1)Compared with the model group, the masculine drug and the investigational drug groups’ rats’neurological signs are improved after one and three days’ administration, and the neurological deficit scoreare declined.
(2)Compared with the model group, the masculine drug and the investigational drug groups’ rats’cerebral hemorrhage area ratio are declined after one and three days’ administration, which has thestatistical significance(P<0.01).
(3)Compared with the model group, the masculine drug and the investigational drug groups’ rats’ brainwater content are declined markedly, which has the statistical significance(P<0.01).
(4)At the third day of administration, compared with the model group, the high-dose and medium-doseinvestigational drug groups’ damaged brain area’s BDNF masculine cells’ quantity are clearlyincreased(P<0.01,P<0.05). At the seventh day after administration, compared with the model group, themasculine drug and all doses’ groups’ damaged brain area’s BDNF masculine cells quantity are clearlyincreased(P<0.001,P<0.01,P<0.05). At the fourteenth day after administration, compared with the shamoperation group, the high and medium-dose of the investigational drug group’s damaged brain area’s BDNFmasculine cells’ quantity are clearly increased(P<0.01,P<0.05).
(5)At the first, the third and the seventh day of the administration, compared with the model group, themasculine drug and low-dose investigational drug groups’ damaged brain area’s NGF masculine cellsquantity are not significantly affected(P>0.05,P>0.05,P>0.05). At the fourteenth day, compared with themodel group, the masculine drug, high and medium-dose group’s damaged brain area’s NGF masculinecells’ quantity are clearly increased(P<0.01,P<0.01).
(6)At the first and third day, compared with the model group, the high and medium-doseinvestigational drug groups’ damaged brain area’s VEGF masculine cells quantity are clearlyincreased(P<0.01,P<0.05); and at the seventh day, compared with the model group the masculine drug, high,medium and low-dose groups’ damaged brain area’s VEGF masculine cells’ quantity are clearlyincreased(P<0.01,P<0.01,P<0.05). At the fourteenth day after administration, compared with the modelgroup, the high and medium-dose groups’ damaged brain area’s VEGF masculine cells’ quantity areclearly increased(P<0.01,P<0.01).
(7)At the first day of administration, compared with the model group, he high-dose investigationaldrug groups’ damaged brain area’s TrkB masculine cells’ quantity are clearly increased(P<0.05). At the third day of administration, compared with the model group, high and medium-dose groups’ damaged brainarea’s TrkB masculine cells’ quantity are clearly increased(P<0.05,P<0.05).At the seventh and fourteenthday, compared with the model group the masculine drug XINGNAOJIAN capsule group’s damaged brainarea’s TrkB masculine cells’ quantity are increased but it is not statistically significant(P>0.05). Theinvestigational drug and medium-dose group all increase the damaged brain area’s TrkB masculine cells’quantity(P<0.01,P<0.05).
(8)Compared with the sham operation group, after seven days’ administration, compared with modelgroup the expression of the masculine drug groups’ BDNFmRNA is increased which is not statisticallysignificant; the high and medium-dose investigational drug groups’ BDNFmRNA expression is clearlyincreased(P<0.01, P<0.01). And the difference of BDNFmRNA expression between low-dose and modelgroups is significant(P<0.05).
(9)After seven days’ administration, the expression of TrkB mRNA is slightly increased between themasculine drug group and model group which don’t show the statistical differences(P>0.05); the high andmedium-dose groups’ expression of TrkB mRNA is increased significantly compared with the modelgroup(P<0.05,P<0.05). But the difference of the expression between low-dose and model group is notsignificant(P>0.05).
Conclusion: The experiment has proved that the intracerebral hemorrhage rats’ neurological deficit,absorption of hematoma and decline of brain water content has been evidently improved by the PoxueHuayu and Tianjing Busui prescription. And it has been proved from the molecular level that themechanism might be that the BDNF, NGF, VEGF’s protein expression surround the hematoma of thecerebral hemorrhage have been increased. The Genetic level mechanism might be that the BDNFmRNAreceptor’s expression which surround the surrounding tissue of the hematoma of the cerebral hemorrhagehas been increased.
引文
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