Aims: Coronary microvascular hyperpermeability is an important contributor to
ischemia or reperfusion (I/R) injury. However, the effective strategy for this insult remains limited. This study aimed to explore the protective effect of the compound Chinese medicine
QiShenYiQi Pills (QSYQ) against coronary microvascular hyperpermeability after cardiac I/R with focusing on the underlying mechanism. Methods and Results: Male Sprague-Dawley rats under
anesthesia were subjected to occlusion of left coronary anterior descending artery followed by reperfusion. QSYQ was administrated 90 min before
ischemia initiation. Human cardiac microvascular endothelial cells (HCMECs) underwent
hypoxia or reoxygenation (H/R) challenge with QSYQ administrated 1 h prior to
hypoxia. QSYQ exhibited effects on attenuating microvascular damage and
albumin leakage after I/R injury, showing a role in maintaining endothelial junctions, caveolae, and
collagen in basement membrane (BM) of microvessels. Study using HCMECs disclosed that QSYQ protected endothelial barrier from impairment by H/R, attenuating the decline of respiratory chain complex I and
ATP synthase, activation of Src/
caveolin-1 and increase of RhoA/ROCK/p-MLC, MMP-9, and CTSS. PP2, a Src inhibitor, partially imitated the effect of QSYQ. Conclusions: The QSYQ was able to prevent I/R-induced cardiac microvascular hyperpermeability via a mechanism involving Src/
caveolin-1 and RhoA/ROCK/MLC signaling.