Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2010, Vol. 8 ›› Issue (5): 465-471.doi: 10.3736/jcim20100511

• Original Experimental Research • Previous Articles     Next Articles

Mechanisms of Chinese herbs combined with ischemic postconditioning in protecting myocardium of rats from ischemia-reperfusion injury

Da-wu Zhang, Lei Zhang, Jian-gang Liu,Cheng-long Wang, Da-zhuo Shi, Ke-ji Chen   

  1. Department of Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
  • Received:2010-01-08 Accepted:2010-03-04 Online:2010-05-20 Published:2010-05-15
  • Contact: Jian-gang Liu


To observe the effects of Chinese patent medicines with the function of replenishing qi to activate blood (RQAB) plus ischemic postconditioning (IPoC) in protecting myocardium of rats from ischemia-reperfusion (I/R) injury, and to explore the possible mechanisms.

Seventy-five Sprague-Dawley rats were randomly divided into sham-operated group (the suture was penetrated around the left anterior descending coronary artery, but not tied, n=15), I/R group (30 minutes of in situ transient occlusion of the left anterior descending artery, followed by 1 hour of reperfusion, n=15), IPoC group (30 minutes occlusion of the left anterior descending artery, followed by 3 cycles of 10 s of reperfusion/10 s of ischemia before 1-hour reperfusion, n=15), RQAB plus IPoC group (pretreated with 0.162 g/kg Xinyue Capsule and 0.135 g/kg Xiongshao Capsule for 14 days, and treated with IPoC 2 h after the final gavage, n=15), fosinopril sodium plus IPoC group (pretreated with fosinopril sodium, 0.9 mg/kg, n=15). Serum creatine kinase-MB (CK-MB) activity and cardiac troponin T (cTnT) level were detected; myocardial infarction size was measured by nitrotetrazolium blue chloride staining; Toll-like receptor 2 (TLR2) and TLR4 in myocardial tissue were examined by immunohistochemical method; interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels in myocardial tissue were examined by enzyme-linked immunosorbant assay.

Compared with the I/R group, myocardial enzymes and infarction size were decreased significantly in the IPoC group (P<0.01); expressions of TLR2 and TLR4 and levels of IL-1β and IL-6 in myocardial tissues were also significantly lower than those in the I/R group (P<0.05). Compared with the fosinopril sodium plus IPoC group, expressions of TLR2 and TLR4 were decreased significantly in the RQAB plus IPoC group (P<0.05, P<0.01). Compared with IPoC, RQAB plus IPoC reduced the infarction size and the release of myocardial enzyme CK-MB (P<0.01), and decreased the expressions of TLR2 and TLR4 and the levels of IL-1β and IL-6 (P<0.05, P<0.01) in myocardial tissues.

Pretreatment with Chinese herbs for nourishing qi and activating blood circulation can enhance the protective effect of IPoC on rat myocardial I/R injury, and its mechanism may be related to inhibition of TLR expression and expressions of the downstream proinflammatory cytokines.

Key words: Replenishing qi to activate blood, Myocardial reperfusion injury, Ischemic postconditioning, Toll-like receptor, Interleukins, Rats

Table 1

Activity of serum CK-MB and content of cTnT in different groups (x±s)"

Group n CK-MB (IU/L) cTnT (jug/L)
Sham-operated 14 693. 64±114. 85 0. 02±0. 01
I/R 11 1 635. 30±229. 20** 4. 41±0. 93〃
IPoC 13 1 222. 39±188. 16**AA 2. 53±0. 51**AA
Fosinopril sodium plus IPoC 13 1 047. 61±223. 13**aaa 2. 36±0. 96〃aa
RQAB plus IPoC 13 967. 10±222. 2. 34±0. 60〃AA

Figure 1

Changes of myocardial infarction size in different groups 1: I/R group (n=5); 2: IPoC group (n=5); 3: Fosinopril sodium plus IPoC group (n=5); 4: RQAB plus IPoC group (n=5). Data were represent as x±s. △△P<0.01, vs I/R group; ▲P<0.05, ▲▲P<0.01, vs IPoC group."


Figure 2

Expression of myocardial TLR2 in different groups detected by immunohistochemical method (Light microscopy, ×200) A: Sham-operated group; B: I/R group; C: IPoC group; D: Fosinopril sodium plus IPoC group; E: RQAB plus IPoC group."

Figure 3

Expression of myocardial TLR4 in different groups detected by immunohistochemical method (Light microscopy, ×200) A: Sham-operated group; B: I/R group; C: IPoC group; D: Fosinopril sodium plus IPoC group; E: RQAB plus IPoC group."

Table 3

Contents of myocardial IL-1β and IL-6 in different groups (x±s, pg/mg)"

Group n IL-ip IL-5
Sham-operated 5 14, 57 土3, 72 14,10 土 1,23
I/R 5 44, SI 士 7,70 ?? 24, 78土 3,47 ??
IPoC 5 33, 67士7,5 20, 57土 1,95
Fosinopril sodium plus IPoC 5 24, 88 士 7,13 19,17±2,44**AA
RQAB plus IPoC 5 24, 33 士 6,14 16,78±1,39AAA
[1] Department of Internal Medicine of Xiyuan Hospital of China Academy of Chinese Medicine, Department of Internal Medicine of Dongzhimen Hospital, Department of Internal Medicine of Guang’anmen Hospital, Department of Internal Medicine of Beijing Xuanwu Hospital. Effective analysis of “antimyocardial infarction herbs” on 118 patients with acute myocardial infarction[J]. Zhonghua Nei Ke Za Zhi, 1976,1(4):212-215
中国中医研究院西苑医院内科, 东直门医院内科, 广安门医院内科, 北京宣武医院内科. 以“抗心梗合剂”为主治疗急性心肌梗塞118例疗效分析[J]. 中华内科杂志, 1976,1(4):212-215
[2] Hou XL, Li BL, Zhao L, Huang SD, Xu ZY, Zhang GX . Effects of Xuefu Zhuyu Capsule on endothelin-1 release in myocardium and vascular endothelium and nitric oxide/nitric oxide synthase system of swines after acute myocardial infarction and reperfusion[J]. J Chin Integr Med, 2008,6(4):381-386
侯霄雷, 李白翎, 赵雷, 黄盛东, 徐志云, 张冠鑫 . 血府逐瘀胶囊对急性心肌梗死再灌注后心肌及内皮素-1、一氧化氮/一氧化氮合酶体系影响的实验研究[J]. 中西医结合学报, 2008,6(4):381-386
[3] He YH, Gu JH, Chen GX, Qiu XM, Zeng XC . Study of Yiqi and Huoxue in protecting rats myocardium with ischemic reperfusion injury[J]. Zhong Xi Yi Jie He Xin Nao Xue Guan Bing Za Zhi, 2007,5(8):707-708
贺运河, 古继红, 陈光贤, 邱晓敏, 曾旭灿 . 益气活血法对大鼠心肌缺血再灌注损伤保护作用的实验研究[J]. 中西医结合心脑血管病杂志, 2007,5(8):707-708
[4] Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, Vinten-Johansen J . Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning[J]. Am J Physiol Heart Circ Physiol, 2003,285(2):H579-H588
doi: 10.1152/ajpheart.01064.2002
[5] Thibault H, Piot C, Staat P, Bontemps L, Sportouch C, Rioufol G, Cung TT, Bonnefoy E, Angoulvant D, Aupetit JF, Finet G , André-Fouët X, Macia JC, Raczka F, Rossi R, Itti R, Kirkorian G, Derumeaux G, Ovize M .Long-term benefit of postconditioning[J]. Circulation, 2008,117(8):1037-1044
doi: 10.1161/CIRCULATIONAHA.107.729780
[6] Dow J, Bhandari A, Kloner RA . The mechanism by which ischemic postconditioning reduces reperfusion arrhythmias in rats remains elusive[J]. J Cardiovasc Pharmacol Ther, 2009,14(2):99-103
doi: 10.1177/1074248408329606
[7] Zatta AJ, Kin H, Lee G, Wang N, Jiang R, Lust R, Reeves JG, Mykytenko J, Guyton RA, Zhao ZQ, Vinten-Johansen J . Infarct-sparing effect of myocardial postconditioning is dependent on protein kinase C signalling[J]. Cardiovasc Res, 2006,70(2):315-324
doi: 10.1016/j.cardiores.2005.11.030
[8] Boyd JH, Mathur S, Wang Y, Bateman RM, Walley KR . Toll-like receptor stimulation in cardiomyocytes decreases contractility and initiates an NF-kappaB dependent inflammatory response[J]. Cardiovasc Res, 2006,72(3):384-393
doi: 10.1016/j.cardiores.2006.09.011
[9] Yang J, Yang J, Ding JW, Chen LH, Wang YL, Li S, Wu H . Sequential expression of TLR4 and its effects on the myocardium of rats with myocardial ischemia-reperfusion injury[J]. Inflammation, 2008,31(5):304-312
doi: 10.1007/s10753-008-9079-x
[10] Shimamoto A, Chong AJ, Yada M, Shomura S, Takayama H, Fleisig AJ, Agnew ML, Hampton CR, Rothnie CL, Spring DJ, Pohlman TH, Shimpo H, Verrier ED . Inhibition of Toll-like receptor 4 with eritoran attenuates myocardial ischemia-reperfusion injury[J]. Circulation, 2006,114(1 Suppl):I270-I274
[11] Sun HY, Wang NP, Kerendi F, Halkos M, Kin H, Guyton RA, Vinten-Johansen J, Zhao ZQ . Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+ overload[J]. Am J Physiol, 2005,288(4):H1900-H1908
[12] Oyama J, Blais C Jr, Liu X, Pu M, Kobzik L, Kelly RA, Bourcier T . Reduced myocardial ischemia-reperfusion injury in toll-like receptor 4-deficient mice[J]. Circulation, 2004,109(6):784-789
doi: 10.1161/01.CIR.0000112575.66565.84
[13] Riad A, Jager S, Sobirey M, Escher F, Yaulema-Riss A, Westermann D, Karatas A, Heimesaat MM, Bereswill S, Dragun D, Pauschinger M, Schultheiss HP , Tschöpe C .Toll-like receptor-4 modulates survival by induction of left ventricular remodeling after myocardial infarction in mice[J]. J Immunol, 2008,180(10):6954-6961
doi: 10.4049/jimmunol.180.10.6954
[14] Sakata Y, Dong JW, Vallejo JG, Huang CH, Baker JS, Tracey KJ, Tacheuchi O, Akira S, Mann DL . Toll-like receptor 2 modulates left ventricular function following ischemia-reperfusion injury[J]. Am J Physiol Heart Circ Physiol, 2007,292(1):H503-H509
doi: 10.1152/ajpheart.00642.2006
[15] Li LZ, Liu JG, Ma LB, Lu XY, Xu H, Xu FQ, Shi DZ, Chen KJ . Effect of Xiongshao Capsule on lipid metabolism and platelet aggregation in experimental atherosclerosis rabbits[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2008,28(12):1100-1103
李立志, 刘剑刚, 马鲁波, 鹿小燕, 徐浩, 徐凤芹, 史大卓, 陈可冀 . 芎芍胶囊对兔动脉粥样硬化模型脂质代谢及血小板聚集的影响[J]. 中国中西医结合杂志, 2008,28(12):1100-1103
[16] Ruan JL, Zhao ZX, Zeng QZ, Qian ZM . Recent advances in study of components and pharmacological roles of Radix Paeoniae Rubra[J]. Zhongguo Yao Li Xue Tong Bao, 2003,19(9):965-970
阮金兰, 赵钟祥, 曾庆忠, 钱忠明 . 赤芍化学成分和药理作用的研究进展[J]. 中国药理学通报, 2003,19(9):965-970
[17] Ding T, Xu HB, Sun XB, Wen FC, Zhou JH, Sun LW, Wei F, Ye DD . Protective effects of Panax quiquefolius saponin on myocardial ischemia[J]. Zhong Yao Yao Li Yu Lin Chuang, 2002,18(4):14-16
丁涛, 徐惠波, 孙晓波, 温富春, 周继胡, 孙利雯, 魏菲, 叶豆丹 . 西洋参茎叶总皂苷对心肌缺血的保护作用[J]. 中药药理与临床, 2002,18(4):14-16
[18] Wang CL, Shi DZ, Yin HJ, Chen KJ . Effect of Panax quiquefolius saponin on angiogenesis and expressions of VEGF and bFGF in myocardium of rats with acute myocardial infarction[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2007,27(4):331-334
王承龙, 史大卓, 殷惠军, 陈可冀 . 西洋参茎叶总皂苷对急性心肌梗死大鼠心肌VEGF、bFGF表达及血管新生的影响[J]. 中国中西医结合杂志, 2007,27(4):331-334
[1] Bing-rong Li, Shi-yun Shao, Long Yuan, Ru Jia, Jian Sun, Qing Ji, Hua Sui, Li-hong Zhou, Yi Zhang, Hui Liu, Qi Li, Yan Wang, Bi-meng Zhang. Effects of mild moxibustion on intestinal microbiome and NLRP3 inflammasome in rats with 5-fluorouracil-induced intestinal mucositis. Journal of Integrative Medicine, 2021, 19(2): 144-157.
[2] Sitthichai Iamsaard, Supatcharee Arun, Jaturon Burawat, Supataechasit Yannasithinon, Saranya Tongpan, Sudtida Bunsueb, Natthapol Lapyuneyong, Pannawat Choowong-in, Nareelak Tangsrisakda, Chadaporn Chaimontri, Wannisa Sukhorum. Evaluation of antioxidant capacity and reproductive toxicity of aqueous extract of Thai Mucuna pruriens seeds. Journal of Integrative Medicine, 2020, 18(3): 265-273.
[3] Morufu Eyitayo Balogun, Elizabeth Enohnyaket Besong, Jacinta Nkechi Obimma, Ogochukwu Sophia Mbamalu, Fankou Serges Athanase Djobissie. Protective roles of Vigna subterranea (Bambara nut) in rats with aspirin-induced gastric mucosal injury. Journal of Integrative Medicine, 2018, 16(5): 342-349.
[4] Lucky Legbosi Nwidu, Raphael Ellis Teme. Hot aqueous leaf extract of Lasianthera africana (Icacinaceae) attenuates rifampicin-isoniazid-induced hepatotoxicity. Journal of Integrative Medicine, 2018, 16(4): 263-272.
[5] Yu-fan Shen, Xue Zhang, Ying Wang, Fan-fan Cao, Georges Uzan, Bin Peng, Deng-hai Zhang. Celastrol targets IRAKs to block Toll-like receptor 4-mediated nuclear factor-κB activation. Journal of Integrative Medicine, 2016, 14(3): 203-208.
[6] Kylie Connolly, Douglas Jackson, Candice Pullen, Andrew Fenning. Alpha-adrenoceptor antagonism by Crassostrea gigas oyster extract inhibits noradrenaline-induced vascular contraction in Wistar rats. Journal of Integrative Medicine, 2015, 13(3): 194-200.
[7] Udhaya Lavinya Baskaran, Sherry Joseph Martin, Rasool Mahaboobkhan, Sabina Evan Prince. Protective role of Triphala, an Indian traditional herbal formulation, against the nephrotoxic effects of bromobenzene in Wistar albino rats. Journal of Integrative Medicine, 2015, 13(2): 115-121.
[8] Hussein O. B. Oloyede, Matthew C. Adaja, Taofeek O. Ajiboye, Musa O. Salawu. Anti-ulcerogenic activity of aqueous extract of Carica papaya seed on indomethacin-induced peptic ulcer in male albino rats. Journal of Integrative Medicine, 2015, 13(2): 105-114.
[9] Anirudha A. Lande, Shirishkumar D. Ambavade, Uma S. Swami, Prafulla P. Adkara Prashant D. Ambavade, Arun B. Waghamare. Saponins isolated from roots of Chlorophytum borivilianum reduce acute and chronic inflammation and histone deacetylase. Journal of Integrative Medicine, 2015, 13(1): 25-33.
[10] Elizabeth Abidemi Balogun, Sylvia Orume Malomo, Joseph Oluwatope Adebayo, Ahmed Adebayo Ishola, Ayodele Olufemi Soladoye, Lawrence Aderemi Olatunji, Olatunji Matthew Kolawole, Stephen Olubunmi Oguntoye, Abiola Samuel Babatunde, Oluwole Busayo Akinola . In vivo antimalarial activity and toxicological effects of methanolic extract of Cocos nucifera (Dwarf red variety) husk fibre. Journal of Integrative Medicine, 2014, 12(6): 504-511.
[11] Urmila Aswar, Mayuri Gurav, Ganesh More, Khaled Rashed, Manoj Aswar. Effect of aqueous extract of Solanum xanthocarpum Schrad. & Wendl. on postmenopausal syndrome in ovariectomized rats. Journal of Integrative Medicine, 2014, 12(5): 439-446.
[12] Benjamin Perry, Junzeng Zhang, Tarek Saleh, Yanwen Wang. Liuwei Dihuang, a traditional Chinese herbal formula, suppresses chronic inflammation and oxidative stress in obese rats. Journal of Integrative Medicine, 2014, 12(5): 447-454.
[13] Xin-fang Zhang, Ji Zhu, Wen-ye Geng, Shu-jun Zhao, Chuan-wei Jiang, Sheng-rong Cai, Miao Cheng, Chuan-yun Zhou, Zi-bing Liu. Electroacupuncture at Feishu (BL13) and Zusanli (ST36) down-regulates the expression of orexins and their receptors in rats with chronic obstructive pulmonary disease. Journal of Integrative Medicine, 2014, 12(5): 417-424.
[14] Upendarrao Golla, Praveen Kumar Gajam, Solomon Sunder Bhimathati. Evaluation of diuretic and laxative activity of hydro-alcoholic extract of Desmostachya bipinnata (L.) Stapf in rats. Journal of Integrative Medicine, 2014, 12(4): 372-378.
[15] Qian Zhang, Xin-hua Xiao, Ming Li, Wen-hui Li, Miao Yu, Hua-bing Zhang, Fan Ping, Zhi-xin Wang, Jia Zheng ​. Chromium-containing traditional Chinese medicine, Tianmai Xiaoke Tablet improves blood glucose through activating insulin-signaling pathway and inhibiting PTP1B and PCK2 in diabetic rats. Journal of Integrative Medicine, 2014, 12(3): 162-170.
Full text



[1] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[2] Hai-feng Wei, Bai-liu Ya, Ling Zhao, Cui-fei Ye, Li Zhang, Lin Li. Evaluation of tongue manifestation of blood stasis syndrome and its relationship with blood rheological disorder in a rat model of transient brain ischemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 73-76
[3] Xi Lin, Jian-ping Liu. Herbal medicines for viral myocarditis. Journal of Chinese Integrative Medicine, 2008, 6(1): 76
[4] Xi Lin, Jian-ping Liu. Tai chi for treating rheumatoid arthritis. Journal of Chinese Integrative Medicine, 2008, 6(1): 82
[5] Liang-ping Hu, Hui Gao. Discrimination of errors in statistical analysis of medical papers published in the first issue of 2006 in Journal of Chinese Integrative Medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 98-106
[6] Yan-bo Zhu , Qi Wang, Cheng-yu Wu, Guo-ming Pang, Jian-xiong Zhao, Shi-lin Shen, Zhong-yuan Xia , Xue Yan . Logistic regression analysis on relationships between traditional Chinese medicine constitutional types and overweight or obesity. Journal of Chinese Integrative Medicine, 2010, 8(11): 1023-1035
[7] Wei Xu, Meng Shi, Jian-gang Liu, Cheng-long Wang . Collagen protein expressions in ischemic myocardium of rats with acute myocardial infarction and effects of qi-tonifying, yin-tonifying and blood-activating herbs and detoxifying and blood-activating herbs. Journal of Chinese Integrative Medicine, 2010, 8(11): 1041-1047
[8] Tao Wang , Feng Qin. Effects of Chinese herbal medicine Xiaoyao Powder on monoamine neurotransmitters in hippocampus of rats with postpartum depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1075-1079
[9] Ying Xu , Chang-chun Zeng , Xiu-yu Cai , Rong-ping Guo , Guang Nie , Ying Jin. Chromaticity and optical spectrum colorimetry of the tongue color in different syndromes of primary hepatic carcinoma. Journal of Chinese Integrative Medicine, 2012, 10(11): 1263-1271
[10] Xiang-ying Mao , Qin Bian , Zi-yin Shen. Analysis of the osteogenetic effects exerted on mesenchymal stem cell strain C3H10T1/2 by icariin via MAPK signaling pathway in vitro. Journal of Chinese Integrative Medicine, 2012, 10(11): 1272-1278