OBJECTIVE

Baicalin, which is isolated from Scutellariae Radix, has been shown to possess therapeutic potential for different diseases. Cardiac microvessel injury in myocardial ischemia-reperfusion (IR) has been extensively explored. However, there have been no studies investigating the physiological regulatory mechanisms of baicalin on nitric oxide production and the necroptosis of cardiac microvascular endothelial cells (CMECs) in myocardial IR injury. This study was designed to investigate the contribution of baicalin to repressing necroptosis and preventing IR-mediated CMEC dysfunction.

MATERIALS AND METHODS

Indicators of ventricular structure and function were measured by an echocardiographic system. An MTT assay was performed to assess cell viability. Nitrite detection was performed to detect nitric oxide content, and cGMP content was determined using a commercially available cGMP complete ELISA kit. Morphology and molecular characteristics were detected by electron micrographs, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting.

RESULT

Our results demonstrated that baicalin significantly improved cardiac function, decreased the myocardial infarction area, and inhibited myocardial cell apoptosis. Moreover, baicalin had a protective effect on cardiac microvessels and promoted the production of nitric oxide (NO) and the level of cGMP in rats that underwent myocardial IR injury. The results of the in vitro experiments showed that baicalin markedly improved cell activity and function in CMECs exposed to hypoxia-reoxygenation (HR). Further experiments indicated that baicalin supplementation suppressed the protein expression of RIP1, RIP3 and p-MLKL to interrupt CMEC necroptosis. In addition, baicalin promoted the production of NO via activating the PI3K-AKT-eNOS signaling pathway. Taken together, our results identified the PI3K-AKT-eNOS axis as a new pathway responsible for reperfusion-mediated microvascular damage.

CONCLUSION

Baicalin protected CMECs in IR rats by promoting the release of NO via the PI3K-AKT-eNOS pathway and mitigated necroptosis by inhibiting the protein expression of RIP1, RIP3 and p-MLKL.