针刺联合微创血肿抽吸术对家兔急性期脑出血灶周围脑组织损伤的影响
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摘要
目的:急性脑出血是一种高死亡率的疾病,其治疗的根本措施是及时清除脑内血肿,控制脑水肿和减轻或逆转血肿周围脑损伤。目前针对血肿本身治疗的研究不多,内科治疗基本上属对症。微创颅内血肿清除治疗能迅速清除血肿,有可能成为最有前途治疗急性脑出血的方法。针刺治疗脑出血的疗效也已为公认,但何时介入治疗还有争议。本文通过传统针刺治疗结合微创血肿抽吸术对家兔脑出血灶周围脑组织损伤的影响的研究,探讨血肿抽吸术结合针刺对于减轻脑出血急性期后脑水肿是否有积极的作用。希望能够为脑出血急性期的临床治疗寻求新的治疗靶点和途径。
方法:选用健康新西兰大白兔65只,雌雄不拘,体重2000-2500克,随机分为4组,假手术组5只,脑出血组20只,血肿抽吸组20只,血肿抽吸+针刺干预组20只。后三组每组再分成6h、24h、3d、7d四个时间点(处死时间),每时间点各5只。参照邹伟和Deinsberger方法进行改良,建立脑出血模型,血肿抽吸组在脑出血模型制作成功后4h,再次麻醉、固定,缓慢向颅内相同部位注入尿激酶50μl(含UK2500u),2h后用1ml注射器轻柔缓慢抽吸,直至抽吸液清亮后缓慢拔出注射器。血肿抽吸加针刺干预组是在脑出血模型制作成功后,于血肿抽吸术结束后立即进行穴位针刺,将实验家兔固定于实验架上,采用“补肾活血、醒脑开窍”针刺法,穴位定位参考《实验针灸学》,对家兔百会、水沟、风府、太阳、血海、太溪、后三里穴进行针刺。分别于制模后6h、24h、3d及7d时称量不同组别脑组织干湿重并计算脑含水量,采用免疫组化法检测各组家兔脑出血灶周围脑组织中基质金属蛋白酶-9(MMP-9)表达的含量,采用明胶酶谱技术检测各组家兔脑出血灶周围组织MMP-9的活性。
结果:脑出血组脑含水量在各观察时间点均较假手术组明显增加,其中以制模后3d时差异尤为显著(P<0.01);血肿抽吸组脑含水量在制模后6h及3d时均较脑出血组明显降低,组间差异均有统计学意义(P<0.01);血肿抽吸+针刺组脑含水最在制模后6h、24h、3d及7d时均较脑出血组明显降低,组间差异均有统计学意义(P<0.05或0.01);血肿抽吸+针刺组脑含水量与血肿抽吸组比较,发现在制模后24h、3d及7d时组间差异均有统计学意义(P<0.05),并以制模后3d时差异尤为显著(P<0.01)。
免疫组化和明胶酶谱结果均显示,脑出血组MMP-9的表达于制模后6h时开始增多,在制模后3d时达到高峰,随后开始减少;脑出血组、血肿抽吸组及血肿抽吸+针刺组3组间比较,发现在制模后6h及24h时MMP-9阳性表达组间差异均无统计学意义(P>0.05);在制模后3d时,血肿抽吸组、血肿抽吸+针刺组MMP-9的表达均较脑出血组明显减少,组间差异均具有统计学意义(P<0.01);并且血肿抽吸+针刺组MMP-9阳性表达较血肿抽吸组进一步降低,组间差异具有统计学意义(P<0.05)。
结论:1.急性脑出血后脑水肿与MMP-9的表达有关;2.血肿抽吸术加针刺干预可以明显减少脑出血后脑组织MMP-9的表达,减轻脑水肿,尤其在第3d时最显著;3.针刺可以用于脑出血急性期。
Objective: Urgent phase of cerebral hemorrhage is a disease of high death rate. The ultimate measure of therapy are purge the haematoma in brain in time, control hydrocephalus and alleviate or reverse brain tissue damnification. Now the research of haematoma itself is not many, the therapy of internal medicine basically belongs to allopathy. The minimally invasive hematoma can prompt purge the haematoma, and is likely to the most prospect therapy method of urgent phase of cerebral hemorrhage. The curative effect of acupuncture had been legalized, but when intervention treatment is still be disputed. The text investigate the effect of acupuncture and minimally invasive hematoma aspiration to rabbit brain tissue damnification in urgent phase of cerebral hemorrhage to discuss whether has positive effect the acupuncture and minimally invasive hematoma for alleviate the hydrocephalus in urgent phase of cerebral hemorrhage or not. Accordingly new target and approach can be provided for the clinic of urgent phase of cerebral hemorrhage.
Methods: A total of 65 healthy New Zealand white rabbits were randomly divided into a sham operation group (SO group, n=5),an intracerebral hemorrhage group (ICH group, n=20), a hematoma aspiration group (HA group, n=20), and an acupuncture and hematoma aspiration group (AHA group, n=20), the last three groups were further divided into groups of 6 hours, 24 hours, 3 days, 7 days(n= 5 in each group). The establishment of cerebral hemorrhage model reference to Zouwei and Deinsberger was produced after the success of 4h, once again anesthetized, the slow part of the intracranial injection of urokinase same 50μl (including UK2500u), 2 hours after the syringe gently with 1ml slow suction, the syringe was slowly pulled. The acupuncture and hematoma aspiration group :adopting nourish kidney, invigorate the circulation of blood and restore consciousness, we choose“Baihui”,“Shuigou”,“Fengfu”,“Taiyang”,“Xuehai”,“Taixi”,“Housanli”. Brain water content(BWC)was measured,and the expression of matrix metalloproteinase-9(MMP-9)in the rabbits’brains was detected by immunohistoehemistry.MMP-9 activity was detected by gelatin zymography.
Results: The brain water content(WBC) of ICH group at every time were more than SO group, and peaked on the 3rd day(P <0.01).The BWC of HA group was obviously slower than ICH group at 6 hours and on the 3rd (P <0.01). The BWC of AHA group was significantly fewer than ICH group on the 6h、24h、3d and 7d(P<0.05 or 0.01).The BWC of AHA group descended significantly more than HA group as time went on(P<0.05),especially on the 3rd day in AHA group(P<0.01).
Both Immunohistochemistry and Gelatin zymography showed that, the expression and activity of MMP-9 in the ICH increased at 6h after ICH and reached a peak at the 3rd day, afterwards, the expression of MMP-9 in ICH group reduced gradually. Compared with ICH group, the expression of MMP-9 in HA group and AHA group reduced at the 3rd day (P <0.01), and the expression of MMP-9 in AHA group reduced more than HA group(P <0.05).
Conclusion: 1.The brain edema after urgent phase of cerebral hemorrhage is relevant to the expression of MMP-9;2.Acupuncture and hematoma aspiration may reduce cerebral hemorrhage in the expression of MMP-9, accordingly alleviate the intracerebral edema;3. Acupuncture can be used in urgent phase of cerebral hemorrhage.
方法:选用健康新西兰大白兔65只,雌雄不拘,体重2000-2500克,随机分为4组,假手术组5只,脑出血组20只,血肿抽吸组20只,血肿抽吸+针刺干预组20只。后三组每组再分成6h、24h、3d、7d四个时间点(处死时间),每时间点各5只。参照邹伟和Deinsberger方法进行改良,建立脑出血模型,血肿抽吸组在脑出血模型制作成功后4h,再次麻醉、固定,缓慢向颅内相同部位注入尿激酶50μl(含UK2500u),2h后用1ml注射器轻柔缓慢抽吸,直至抽吸液清亮后缓慢拔出注射器。血肿抽吸加针刺干预组是在脑出血模型制作成功后,于血肿抽吸术结束后立即进行穴位针刺,将实验家兔固定于实验架上,采用“补肾活血、醒脑开窍”针刺法,穴位定位参考《实验针灸学》,对家兔百会、水沟、风府、太阳、血海、太溪、后三里穴进行针刺。分别于制模后6h、24h、3d及7d时称量不同组别脑组织干湿重并计算脑含水量,采用免疫组化法检测各组家兔脑出血灶周围脑组织中基质金属蛋白酶-9(MMP-9)表达的含量,采用明胶酶谱技术检测各组家兔脑出血灶周围组织MMP-9的活性。
结果:脑出血组脑含水量在各观察时间点均较假手术组明显增加,其中以制模后3d时差异尤为显著(P<0.01);血肿抽吸组脑含水量在制模后6h及3d时均较脑出血组明显降低,组间差异均有统计学意义(P<0.01);血肿抽吸+针刺组脑含水最在制模后6h、24h、3d及7d时均较脑出血组明显降低,组间差异均有统计学意义(P<0.05或0.01);血肿抽吸+针刺组脑含水量与血肿抽吸组比较,发现在制模后24h、3d及7d时组间差异均有统计学意义(P<0.05),并以制模后3d时差异尤为显著(P<0.01)。
免疫组化和明胶酶谱结果均显示,脑出血组MMP-9的表达于制模后6h时开始增多,在制模后3d时达到高峰,随后开始减少;脑出血组、血肿抽吸组及血肿抽吸+针刺组3组间比较,发现在制模后6h及24h时MMP-9阳性表达组间差异均无统计学意义(P>0.05);在制模后3d时,血肿抽吸组、血肿抽吸+针刺组MMP-9的表达均较脑出血组明显减少,组间差异均具有统计学意义(P<0.01);并且血肿抽吸+针刺组MMP-9阳性表达较血肿抽吸组进一步降低,组间差异具有统计学意义(P<0.05)。
结论:1.急性脑出血后脑水肿与MMP-9的表达有关;2.血肿抽吸术加针刺干预可以明显减少脑出血后脑组织MMP-9的表达,减轻脑水肿,尤其在第3d时最显著;3.针刺可以用于脑出血急性期。
Objective: Urgent phase of cerebral hemorrhage is a disease of high death rate. The ultimate measure of therapy are purge the haematoma in brain in time, control hydrocephalus and alleviate or reverse brain tissue damnification. Now the research of haematoma itself is not many, the therapy of internal medicine basically belongs to allopathy. The minimally invasive hematoma can prompt purge the haematoma, and is likely to the most prospect therapy method of urgent phase of cerebral hemorrhage. The curative effect of acupuncture had been legalized, but when intervention treatment is still be disputed. The text investigate the effect of acupuncture and minimally invasive hematoma aspiration to rabbit brain tissue damnification in urgent phase of cerebral hemorrhage to discuss whether has positive effect the acupuncture and minimally invasive hematoma for alleviate the hydrocephalus in urgent phase of cerebral hemorrhage or not. Accordingly new target and approach can be provided for the clinic of urgent phase of cerebral hemorrhage.
Methods: A total of 65 healthy New Zealand white rabbits were randomly divided into a sham operation group (SO group, n=5),an intracerebral hemorrhage group (ICH group, n=20), a hematoma aspiration group (HA group, n=20), and an acupuncture and hematoma aspiration group (AHA group, n=20), the last three groups were further divided into groups of 6 hours, 24 hours, 3 days, 7 days(n= 5 in each group). The establishment of cerebral hemorrhage model reference to Zouwei and Deinsberger was produced after the success of 4h, once again anesthetized, the slow part of the intracranial injection of urokinase same 50μl (including UK2500u), 2 hours after the syringe gently with 1ml slow suction, the syringe was slowly pulled. The acupuncture and hematoma aspiration group :adopting nourish kidney, invigorate the circulation of blood and restore consciousness, we choose“Baihui”,“Shuigou”,“Fengfu”,“Taiyang”,“Xuehai”,“Taixi”,“Housanli”. Brain water content(BWC)was measured,and the expression of matrix metalloproteinase-9(MMP-9)in the rabbits’brains was detected by immunohistoehemistry.MMP-9 activity was detected by gelatin zymography.
Results: The brain water content(WBC) of ICH group at every time were more than SO group, and peaked on the 3rd day(P <0.01).The BWC of HA group was obviously slower than ICH group at 6 hours and on the 3rd (P <0.01). The BWC of AHA group was significantly fewer than ICH group on the 6h、24h、3d and 7d(P<0.05 or 0.01).The BWC of AHA group descended significantly more than HA group as time went on(P<0.05),especially on the 3rd day in AHA group(P<0.01).
Both Immunohistochemistry and Gelatin zymography showed that, the expression and activity of MMP-9 in the ICH increased at 6h after ICH and reached a peak at the 3rd day, afterwards, the expression of MMP-9 in ICH group reduced gradually. Compared with ICH group, the expression of MMP-9 in HA group and AHA group reduced at the 3rd day (P <0.01), and the expression of MMP-9 in AHA group reduced more than HA group(P <0.05).
Conclusion: 1.The brain edema after urgent phase of cerebral hemorrhage is relevant to the expression of MMP-9;2.Acupuncture and hematoma aspiration may reduce cerebral hemorrhage in the expression of MMP-9, accordingly alleviate the intracerebral edema;3. Acupuncture can be used in urgent phase of cerebral hemorrhage.
引文
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