Baicalin protects the myocardium from reperfusion‑induced damage in isolated rat hearts via the antioxidant and paracrine effect

Kong,Feng; Luan,Yun; Zhang,Zhao‑Hua; Cheng,Guang‑Hui; Qi,Tong‑Gang; Sun,Chao

doi:10.3892/etm.2013.1369

Baicalin protects the myocardium from reperfusion‑induced damage in isolated rat hearts via the antioxidant and paracrine effect

Authors:
- Feng Kong
- Yun Luan
- Zhao‑Hua Zhang
- Guang‑Hui Cheng
- Tong‑Gang Qi
- Chao Sun
View Affiliations

Affiliations: Central Research Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Department of Pediatrics, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China
Published online on: October 29, 2013 https://doi.org/10.3892/etm.2013.1369
Pages: 254-259

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to investigate the protective effect of baicalin (BA) against ischemia‑reperfusion (I/R) injury in isolated rat hearts. Sprague‑Dawley rat hearts were rapidly removed, mounted on a Langendorff apparatus and subjected to 30 min ischemia followed by 30 min reperfusion with Krebs‑Henseleit (K‑H) solution at 37˚C to establish the isolated I/R injury model. All animals (n=50) were randomly divided into five groups (n=10 in each): I, normal control; II, I/R; III, I/R plus 20 mg/kg BA; IV, I/R plus 40 mg/kg BA; and V, I/R plus 80 mg/kg BA. The degree of heart injury caused by the I/R was assessed by evaluating left ventricular function and by detecting the levels of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary effluent and the myocardial superoxide dismutase (SOD) and malondialdehyde (MDA) levels in the isolated rat hearts. Myocardial infarct size and vascular density were assessed using histology and immunohistochemistry. The apoptotic cardiomyocytes were determined using flow cytometry (FCM). Compared with group II, the BA groups demonstrated improved left ventricular function, reduced CK and LDH release in the coronary effluent and increased SOD and MDA activity (P<0.05). Furthermore, histology and immunohistochemistry results showed that the infarct size was reduced and vessel density was augmented in the BA groups (P<0.01) compared with group II. The FCM results indicated that apoptosis was significantly lower in the BA groups than in group II (P<0.05) and that the protective effect was dose‑dependent. In conclusion, these results demonstrated that BA exerts a dose‑dependent protective effect on I/R injury in isolated rat hearts, the mechanisms of which may be associated with antioxidant and anti‑apoptosis properties. To the best of our knowledge, this study is the first evaluation of the efficacy of BA in isolated rat hearts using histology and immunohistochemistry, providing a foundation for the use of BA in the treatment of acute myocardial infarction.

View Figures

View References

1	Garg HK and Bryan NS: Dietary sources of nitrite as a modulator of ischemia/reperfusion injury. Kidney Int. 75:1140–1144. 2009.PubMed/NCBI
2	Xiao CY, Yuhki K, Hara A, et al: Prostaglandin E2 protects the heart from ischemia-reperfusion injury via its receptor subtype EP4. Circulation. 109:2462–2468. 2004. View Article : Google Scholar : PubMed/NCBI
3	Zhang WH, Fu SB, Lu FH, et al: Involvement of calcium-sensing receptor in ischemia/reperfusion-induced apoptosis in rat cardiomyocytes. Biochem Biophys Res Commun. 347:872–881. 2006. View Article : Google Scholar : PubMed/NCBI
4	Wang YL, Wang CY, Zhang BJ and Zhang ZZ: Shenfu injection suppresses apoptosis by regulation of Bcl-2 and caspase-3 during hypoxia/reoxygenation in neonatal rat cardiomyocytes in vitro. Mol Biol Rep. 36:365–370. 2009. View Article : Google Scholar : PubMed/NCBI
5	Eefting F, Rensing B, Wigman J, Pannekoek WJ, Liu WM, Cramer MJ, Lips DJ and Doevendans PA: Role of apoptosis in reperfusion injury. Cardiovasc Res. 61:414–426. 2004. View Article : Google Scholar : PubMed/NCBI
6	Dumont EA, Hofstra L, van Heerde WL, et al: Cardiomyocyte death induced by myocardial ischemia and reperfusion: measurement with recombinant human annexin-V in a mouse model. Circulation. 102:1564–1568. 2000. View Article : Google Scholar : PubMed/NCBI
7	Borutaite V, Jekabsone A, Morkuniene R and Brown GC: Inhibition of mitochondrial permeability transition prevents mitochondrial dysfunction, cytochrome c release and apoptosis induced by heart ischemia. J Mol Cell Cardiol. 35:357–366. 2003. View Article : Google Scholar
8	Gao Z, Huang K, Yang X and Xu H: Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim Biophys Acta. 1472:643–650. 1999. View Article : Google Scholar : PubMed/NCBI
9	Dethlefsen SM, Sherpo D and D’Amore P: Arachindonic acid metabolites in bFGF-, PDGF-, and serum-stimulated vascular cell growth. Exp Cell Res. 212:262–273. 1994. View Article : Google Scholar : PubMed/NCBI
10	Li BQ, Fu T, Dongyan Y, Mikovits JA, Ruscetti FW and Wang JM: Flavonoid baicalin inhibits HIV-1 infection at the level of viral entry. Biochem Biophys Res Commun. 276:534–538. 2000. View Article : Google Scholar : PubMed/NCBI
11	Chou TC, Chang LP, Li CY, Wong CS and Yang SP: The antiinflammatory and analgesic effects of baicalin in carrageenan-evoked thermal hyperalgesia. Anesth Analg. 97:1724–1729. 2003. View Article : Google Scholar : PubMed/NCBI
12	Lin CC and Shieh DE: The anti-inflammatory activity of Scutellaria rivularis extracts and its active components, baicalin, baicalein and wogonin. Am J Chin Med. 24:31–36. 1996.
13	Kubo M, Matsuda H, Tanaka M, Kimura Y, Okuda H, Higashino M, Tani T, Namba K and Arichi S: Studies on Scutellariae radix. VII. Anti-arthritic and anti-inflammatory actions of methanolic extract and flavonoid components from Scutellariae radix. Chem Pharm Bull (Tokyo). 32:2724–2729. 1984. View Article : Google Scholar : PubMed/NCBI
14	Xiping Z, Hua T, Hanqing C, Li C, Zhiwei W, Keyi W, Wei Y, Yun L, Qingyu L, Qing H and Fei W: The protecting effects and mechanisms of Baicalin and Octreotide on heart injury in rats with SAP. Mediators Inflamm. 2007:194692007. View Article : Google Scholar : PubMed/NCBI
15	Woo AY, Cheng CH and Waye MM: Baicalein protects rat cardiomyocytes from hypoxia/reoxygenation damage via a prooxidant mechanism. Cardiovasc Res. 65:244–253. 2005. View Article : Google Scholar : PubMed/NCBI
16	Lin L, Wu XD, Davey AK and Wang J: The anti-inflammatory effect of baicalin on hypoxia/reoxygenation and TNF-alpha induced injury in cultural rat cardiomyocytes. Phytother Res. 24:429–437. 2010. View Article : Google Scholar : PubMed/NCBI
17	Reichelt ME, Willems L, Hack BA, Peart JN and Headrick JP: Cardiac and coronary function in the Langendorff-perfused mouse heart model. Exp Physiol. 94:54–70. 2009. View Article : Google Scholar : PubMed/NCBI
18	Yamashiro S, Kuniyoshi Y, Arakaki K, Uezu T, Miyagi K and Koja K: Cardioprotective effects of tetrahydrobiopterin in cold heart preservation after cardiac arrest. Ann Thorac Cardiovasc Surg. 12:95–104. 2006.PubMed/NCBI
19	Yamashiro S, Noguchi K, Matsuzaki T, Miyagi K, Nakasone J and Sakanashi M, Koja K and Sakanashi M: Beneficial effect of tetrahydrobiopterin on ischemia-reperfusion injury in isolated perfused rat hearts. J Thorac Cardiovasc Surg. 124:775–784. 2002. View Article : Google Scholar : PubMed/NCBI
20	Luan Y, Liu XC, Zhang GW, Shi RF, Zhao XB, Zhao CH, Liu TJ, Lü F, Yang Q and He GW: Mid-term effect of stem cells combined with transmyocardial degradable stent on swine model of acute myocardial infarction. Coron Artery Dis. 21:233–243. 2010. View Article : Google Scholar : PubMed/NCBI
21	Wang Y, Liu XC, Zhang GW, et al: A new transmyocardial degradable stent combined with growth factor, heparin, and stem cells in acute myocardial infarction. Cardiovasc Res. 84:461–469. 2009. View Article : Google Scholar : PubMed/NCBI
22	Slama P, Sladek Z, Rysanek D and Langrova T: Effect of Staphylococcus aureus and Streptococcus uberis on apoptosis of bovine mammary gland lymphocytes. Res Vet Sci. 87:233–238. 2009.
23	Ouyang HC, Wu JL and Chen JH: Protective effect of baicalin aganist myocardial ischemia and reperfusion injury in rats. Chin J New Drugs Clin Rem. 256:408–412. 2006.(In Chinese).
24	Shao ZH, Vanden Hoek TL, Qin Y, Becker LB, Schumacker PT, Li CQ, Dey L, Barth E, Halpern H, Rosen GM and Yuan CS: Baicalein attenuates oxidant stress in cardiomyocytes. Am J Physiol Heart Circ Physiol. 282:H999–H1006. 2002.PubMed/NCBI
25	Zhang Z, Yu B and Tao GZ: Apelin protects against cardiomyocyte apoptosis induced by glucose deprivation. Chin Med J (Engl). 122:2360–2365. 2009.PubMed/NCBI
26	Mani K: Programmed cell death in cardiac myocytes: strategies to maximize post-ischemic salvage. Heart Fail Rev. 13:193–209. 2008. View Article : Google Scholar : PubMed/NCBI
27	Kang PM and Izumo S: Apoptosis in heart: basic mechanism and implications in cardiovascular diseases. Trends Mol Med. 9:177–182. 2003. View Article : Google Scholar : PubMed/NCBI
28	Saraste A, Voipio-Pulkki LM, Parvinen M and Pulkki K: Apoptosis in the heart. N Engl J Med. 336:1025–1026. 1997. View Article : Google Scholar : PubMed/NCBI
29	Kim NH and Kang PM: Kang: Apoptosis in cardiovascular diseases: mechanism and clinical implications. Korean Circ J. 40:299–305. 2010. View Article : Google Scholar : PubMed/NCBI
30	Umansky SR, Shapiro JP, Cuenco GM, Foehr MW, Bathurst IC and Tomei LD: Prevention of rat neonatal cardiomyocyte apoptosis induced by simulated in vitro ischemia and reperfusion. Cell Death Differ. 4:608–616. 1997. View Article : Google Scholar : PubMed/NCBI
31	Hofstra L, Liem IH, Dumont EA, Boersma HH, van Heerde WL, Doevendans PA, De Muinck E, Wellens HJ, Kemerink GJ, Reutelingsperger CP and Heidendal GA: Visualisation of cell death in vivo in patients with acute myocardial infarction. Lancet. 356:209–212. 2000. View Article : Google Scholar : PubMed/NCBI