Abstract��OBJECTIVE To explore the protection mechanism of orthogonal compatibility of puerarin(A),ligustrazine(B), astragaloside IV(C) and catalpolon(D),the main active ingredients from yangyin tongnao granules, on SD rats damaged by ischemic reperfusion injury, and select the optimal combination. METHODS SD rats were randomly divided into sham operation group, model group, orthogonal compatibility group and positive control group. The rat middle cerebral artery occlusion (MCAO) model was established. The compatibility of components was arranged by L9(34) orthogonal design. The symptoms of neurological deficit in rats and the pathological changes in hippocampus were observed; TTC staining was used to detect the cerebral infarction volume. IHC was used to evaluate the expression of NLRP3 protein ischemic brain tissue. RT-PCR was used to detect the expressions of ASC, caspase-1, IL-1, mRNA, IL-18 and MMP-9 in the hippocampal of brain tissue. The RESULTS of orthogonal test were analyzed by range analysis. RESULTS The orthogonal combination groups could effectively improve neurological deficits in cerebral ischemia reperfusion injury, reduce infarction volume, inhibit the expression of NLRP3 inflammasome, decrease the expression of ASC, caspase-1, IL-1, IL-18 and MMP-9. The analysis of test results showed that the combination with ligustrazine 100 mg��kg-1,puerarin 20 mg��kg-1, astragaloside �� 80 mg��kg-1 and catalpol 20 mg��kg-1 was the superior one. CONCLUSION The main active ingredients combination of yangyin tongnao granules played a protective mechanism on focal cerebral ischemia reperfusion injury rats. Its mechanism might be related to inhibition of NLRP3 inflammasome,down-regulation of ASC, caspase-1, IL-1, IL-18 and MMP-9.
����, ����, ����, ���۾�, ����, ����, �ܻݷ�, ��ͬ. ����ͨ�Կ�����Ч�ɷ��������ȱѪ�ٹ�ע���˴������û��Ƶ��о�[J]. �й�ҩѧ��־, 2018, 53(3): 199-204.
RONG Yan, HE Yu, CHENG Lan, WANG Hui-jun, YU Li, YANG Jie-hong, ZHOU Hui-fen, WAN Hai-tong. Protection Mechanism of the Main Active Ingredients Combination of Yangyin Tongnao Granules on Cerebral Ischemia/Reperfusion Injury Rats. Chinese Pharmaceutical Journal, 2018, 53(3): 199-204.
L�� Z G, XIE Y M, LI M Q, et al. Reasonable application of traditional Chinese medicines injections promoting blood circulation and removing blood stasis in treating ischemic cerebrovascular diseases [J]. China J Chin Mater Med (�й���ҩ��־), 2012, 37(22): 3494-3499.
[2]
ZHANG H Y, WANG J P. Research advances on the usage of traditional Chinese medicine for stroke [J]. J China Pharm(�й�ҩ��), 2010, 21(3): 276-278.
[3]
LIU Q Y, SONG J, CHEN K J. Research progress of traditional Chinese medicine in treatment of ischemic stroke [J]. Chin J Integr Tradit West Med (�й�����ҽ�����־), 2000, 20(4): 309-312.
[4]
RONG Y, ZHANG Y Y, YANG J H, et al. Impact of Yangyin Tongnao Keli on hippocampus endoplasmic reticulum stress in rats with cerebral ischemia reperfusion injury [J]. J Tradit Chin Med (��ҽ��־), 2017, 58(5): 405-409.
[5]
DU Y G, WAN H T, MENG X L, et al. Study of matrix metalloproteinase 9 expression after mice ischemia /reperfusion in hippocampus and treatment effects of Yangyin Tongnao granule [J]. Chin J Tradit Chin Med West Med Crit Care (�й�����ҽ��ϼ�����־), 2003, 10(6): 330-332.
[6]
ZHU X X, MEI Q B, WANG Y M, et al. Mechanism of Yangyintongnao particle increase cerebral blood flow [J]. J Fourth Mil Med Univ (���ľ�ҽ��ѧѧ��),2001, 22(14):1276-1278.
[7]
LONGA E Z, WEINSTEIN P R, CARLSON S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats [J]. Stroke, 1989, 20(1): 84-91.
[8]
WAN H T, BIE X D, YAO Z, et al. Treating ischemic stroke patients of deficiency of Qi and Yin syndrome and static blood obstructing collaterals syndrome by Yangyin Yiqi Huoxue recipe: a clinical study of therapeutic effect [J]. Chin J Integr Tradit West Med (�й�����ҽ�����־), 2015, 35(3): 281-286.
[9]
ZHANG B. Clinical observation of Yiqi Huoxue Tongnao Decoction in treating convalescent ischemic stroke [J]. Shanghai J Tradit Chin Med (�Ϻ���ҽҩ��־), 2010, 44(1): 41-42.
[10]
CHEN W. The research on the immune pathogenesy and regulation of myocardial injury after skeletal muscle ischemia reperfusion [D]. Beijing:The Chinese People��s Liberation Army (PLA) School of Medicine,2013.
[11]
YIN P, LIU X W. The expression and clinical implication of TLR3 in myocardial ischemia -reperfusion injury of rat model [J]. Immunol J(����ѧ��־), 2014, 30(9): 768-772, 791.
[12]
ZHANG N, ZHANG X J, LIU X X, et al. Chrysophanol inhibits nalp3 inflammasome activation and ameliorates cerebral ischemia/reperfusion in mice [J]. Med Inflamm, 2014, 2014:370530. doi: 10.1155/2014/370530.
2018, Vol. 53 
