Abstract
The therapeutic potential of QiShenYiQi Pills on gastrorrhagia caused by aspirin and clopidogrel in rats

Objectives: Antiplatelet therapy using Aspirin (ASA) and clopidogrel (CLP) combination can cause gastrointestinal bleeding, limiting its long-term use and posing an unresolved clinical issue. This study aims to investigate the protective effects and possible mechanisms of the traditional Chinese medicine compound QishenYiqi (QSYQ) Pills on the gastrorrhagia induced by ASA and CLP.

Methods: Male SD rats were daily given ASA and CLP for four consecutive weeks to establish a gastrorrhagia model. To explore the therapeutic effect of QSYQ, treatment group of rats was given ASA+CLP along, or together with QSYQ. The normal control group was given an equal amount of physiological saline daily. After the administration, gastric bleeding, hemoglobin content in gastric tissue, and Evans blue extravasation in gastric tissue were examined; H&E staining and microscopy were used to examine the morphology of microvessels in the gastric mucosa; immunofluorescence staining and two-photon microscopy were used to observe the distribution of tight junction proteins Claudin-5, Occludin, and basement membrane collagen proteins Collagen IV and Laminin in microvascular endothelial cells of the gastric mucosa; ELISA was used to detect malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), mitochondrial complex I, II, IV, V, and the content of ATP, AMP, and ADP; Western Blot was used to detect the expression of tight junction proteins Claudin-5, Occludin, junction adhesion molecule (JAM-1), vascular endothelial cadherin (VE-Cadherin), Collagen IV, and Laminin.

Results: QSYQ significantly decreased gastric mucosal microvascular bleeding, reduced the hemoglobin content and Evans blue extravasation in gastric tissue induced by the combined use of ASA and CLP; significantly suppressed the abnormal distribution and rupture of tight junction proteins Claudin-5 and Occludin in gastric mucosal microvascular endothelium; upregulated the expression of Claudin-5, JAM-1, Occludin, and VE-Cadherin in gastric tissue extracts, increased the ratio of ATP/AMP and ATP/ADP, upregulated the activity of mitochondrial complexes I and V, and the expression of subunits ATP-β and ATP-5D.

Conclusion: QSYQ can inhibit gastric mucosal microvascular bleeding induced by the combined use of ASA and CLP in rats. This effect is reflected by the improved activity of mitochondrial complexes I and V, upregulation of the expression of subunits ATP-β and ATP-5D, improvement of energy metabolism; inhibition of low expression and disordered arrangement of tight junctions in endothelial cells; and inhibition of basement membrane destruction