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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

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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