The Effects and Mechanism of Scutellaria baicalensis Georgi Stems and Leaves Flavonoids on Myelin Sheath Degeneration Induced by Composite Aß in Rats.

BACKGROUND: Alzheimer's disease is a degenerative disease of the central nervous system, and its characteristic pathological changes are closely associated with Aß deposition and neurofibrillary tangles. Many studies have found that malignant changes in the myelin sheath and oligodendrocyte (OL) are accompanied by the occurrence and development of AD. Therefore, any method that can resist myelin sheath and OL disorders may be a potential strategy for AD. OBJECTIVE: To investigate the effects and mechanism of Scutellaria baicalensis Georgi stem and leaf flavonoids (SSFs) on the myelin sheath degeneration induced by Aß25-35 combined with AlC13 and RHTGF-ß1 (composite Aß) in rats. METHODS: A rat AD model was established by intracerebroventricular injection of composite Aß. The Morris water maze was used to screen the memory impairment rat model. The successful model rats were divided into the model group and the 35, 70, and 140 mg/kg SSFS groups. The myelin sheath changes in the cerebral cortex were observed with an electron microscope. The expression of the oligodendrocyte- specific protein claudin 11 was detected with immunohistochemistry. The protein expression levels of myelin oligodendrocyte glycoprotein (MOG), myelin-associated glycoprotein (MAG) and myelin basic protein (MBP), sphingomyelin synthase-1 (SMS1), and sphingomyelinase-2 (SMPD2) were assayed by Western blotting. RESULTS: The intracerebroventricular injection of composite Aß caused degeneration of the myelin sheath structure and was accompanied by the decreased claudin 11, MOG, MAG, MBP, and SMS1, and increased SMPD2 protein expression in the cerebral cortex. However, 35, 70, and 140 mg/kg SSFs can differentially ameliorate the above abnormal changes induced by composite Aß. CONCLUSION: SSFs can alleviate myelin sheath degeneration and increase the protein expression of claudin 11, MOG, MAG, and MBP, and the effective mechanism may be related to the positive regulation of SMS1 and SMPD2 activities.

Cigarette Smoke or Motor Vehicle Exhaust Exposure Induces PD-L1 Upregulation in Lung Epithelial Cells in COPD Model Rats.

A high smoking-independent chronic obstructive pulmonary disease (COPD) prevalence is observed in lung cancer patients. However, the underlying connection between these two diseases still remains unclear. Cigarette smoking and ambient air pollution are common risk factors for COPD and lung cancer. In this study, we established rat COPD model through exposure to cigarette smoke (CS) or motor vehicle exhaust (MVE). The model rats developed COPD-like phenotypes, manifested as lung functions decline, lung inflammation, emphysema-like alveolar enlargement and airway remodeling. The programmed death-ligand 1 (PD-L1), a factor contributing to immune escape of tumor cells, was overexpressed in lungs from COPD model rats, though more severe COPD phenotypes did not bring with further PD-L1 overexpression in lung. The upregulations of proinflammatory cytokines and PD-L1 were also observed in cultured human bronchial epithelial cells BEAS-2B upon treatment with cigarette smoke extract (CSE) or diesel-related particulate matter 2.5 (PM2.5, SEM1650b). The inflammatory cytokines produced in BEAS-2B cells reflected the PD-L1 levels. Furthermore, ERK1/2, a kinase mediating PD-L1 upregulation in premalignant bronchial cells or NSCLC cells, and STAT1/3, which was reportedly associated with PD-L1 expression in lung tumors, were activated in COPD rats' lungs or in BEAS-2B cells treated with CSE or PM2.5. Therefore, we proposed that inflammation associated PD-L1 overexpression in airway epithelial cells could be the underlying factor facilitating lung cancer incidence in COPD.