Effects of acupuncture at GV20 and ST36 on the expression of matrix metalloproteinase 2, aquaporin 4, and aquaporin 9 in rats subjected to cerebral ischemia/reperfusion injury.
OBJECTIVE
Ischemic stroke is characterized by high morbidity and mortality worldwide. Matrix metalloproteinase 2 (MMP2), aquaporin (AQP) 4, and AQP9 are linked to permeabilization of the blood-brain barrier (BBB) in cerebral ischemia/reperfusion injury (CIRI). BBB disruption, tissue inflammation, and MMP/AQP upregulation jointly provoke brain edema/swelling after CIRI, while acupuncture and electroacupuncture can alleviate CIRI symptoms. This study evaluated the hypothesis that acupuncture and electroacupuncture can similarly exert neuroprotective actions in a rat model of middle cerebral artery occlusion (MCAO) by modulating MMP2/AQP4/APQ9 expression and inflammatory cell infiltration.


METHODS
Eighty 8-week-old Sprague-Dawley rats were randomly divided into sham group S, MCAO model group M, acupuncture group A, electroacupuncture group EA, and edaravone group ED. The MCAO model was established by placement of a suture to block the middle carotid artery, and reperfusion was triggered by suture removal in all groups except group S. Acupuncture and electroacupuncture were administered at acupoints GV20 (governing vessel-20) and ST36 (stomach-36). Rats in groups A, EA, and ED received acupuncture, electroacupuncture, or edaravone, respectively, immediately after MCAO. Neurological function (assessed using the Modified Neurological Severity Score), infarct volume, MMP2/AQP4/AQP9 mRNA and protein expression, and inflammatory cell infiltration were all evaluated at 24 h post-reperfusion.


RESULTS
Acupuncture and electroacupuncture significantly decreased infarct size and improved neurological function. Furthermore, target mRNA and protein levels and inflammatory cell infiltration were significantly reduced in groups A, EA, and ED vs. group M. However, MMP2/AQP levels and inflammatory cell infiltration were generally higher in groups A and EA than in group ED except MMP2 mRNA levels.


CONCLUSIONS
Acupuncture and electroacupuncture at GV20 and ST36 both exercised neuroprotective actions in a rat model of MCAO, with no clear differences between groups A and EA. Therefore, acupuncture and electroacupuncture might find utility as adjunctive and complementary treatments to supplement conventional therapy for ischemic stroke.
Department of Traditional Chinese Medicine, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College (PUMC), Chinese Academy of Medical Sciences, Beijing, China.
Hong
H
Xu
Department of Traditional Chinese Medicine, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College (PUMC), Chinese Academy of Medical Sciences, Beijing, China.
Yamin
Y
Zhang
Department of Traditional Chinese Medicine, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College (PUMC), Chinese Academy of Medical Sciences, Beijing, China.
Hua
H
Sun
Department of Traditional Chinese Medicine, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College (PUMC), Chinese Academy of Medical Sciences, Beijing, China.
Suhui
S
Chen
Department of Traditional Chinese Medicine, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College (PUMC), Chinese Academy of Medical Sciences, Beijing, China.
Fuming
F
Wang
D015669:Acupuncture Points; D015670:Acupuncture Therapy / Q000379:methods; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D020346:Aquaporins / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001929:Brain Edema / Q000378:metabolism / Q000628:therapy; D002545:Brain Ischemia / Q000378:metabolism* / Q000628:therapy; D004195:Disease Models, Animal; D015671:Electroacupuncture / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000628:therapy; D007249:Inflammation / Q000378:metabolism / Q000628:therapy; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000628:therapy
C496032:Aqp4 protein, rat; C491637:Aqp9 protein, rat; D051401:Aquaporin 4; D020346:Aquaporins; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat