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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 E-mail:liujiangang2002@sina.com

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Objective

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.
Methods

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.
Results

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.
Conclusion

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
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