This study explores the reparative effect of Qixiong Zuogui Compound Prescription(QXZG) intervention on the blood-brain barrier(BBB) in the aging brain with middle cerebral artery occlusion(MCAO) in rats mediated by bone marrow stem cells(BMSCs)-derived exosomes, as well as its anti-aging mechanism. An aging MCAO composite model was established using D-galactose-induced aging combined with line embolism. Rats were divided into young sham surgery group, aging sham surgery group, model group, exosome group, and exosome with traditional Chinese medicine(TCM) intervention group. SA-β-gal staining combined with TTC staining were used to evaluate the model establishment. Exosomes group or exosomes with TCM intervention group were injected via the tail vein 2 h post-surgery and 48 and 96 h post-ischemia reperfusion. Neurological deficit scores were assessed at 2 h, 3 d, and 7 d post-modeling. Cognitive function was evaluated using novel object recognition tests on the 7th day, and brain infarct volume was observed via MRI. Evans Blue staining was used to evaluate BBB permeability. Western blot was performed to detect the expression of tight junction proteins ZO-1 and Occludin in brain tissue. ELISA was used to measure serum matrix metalloproteinase(MMP)-9 and MMP-2 levels. SA-β-gal staining was used to assess cellular senescence. RT-qPCR was performed to detect p21 mRNA expression, and qPCR was used to measure relative telomere length. The results showed that QXZG intervention-derived BMSCs exosomes significantly reduced brain infarct volume in aging MCAO rats, improved neurological deficit scores, and enhanced cognitive function. These exosomes suppressed MMP-2 and MMP-9 expression, promoted he expression of tight junction proteins ZO-1 and Occludin, reduced BBB permeability, lowered p21 mRNA expression, elongated telomeres, and delayed cell senescence. In conclusion, this study confirms that QXZG intervention-derived BMSC exosomes may repair the BBB by reducing MMP-2 and MMP-9 levels and increasing ZO-1 and Occludin expression. Moreover, its anti-aging mechanism may involve reducing p21 mRNA expression and limiting telomere shor-tening.
Keywords: Qixiong Zuogui Compound Prescription; aging; blood-brain barrier; bone marrow stem cell; exosomes; stroke.