Bufei Jianpi granules improve skeletal muscle and mitochondrial dysfunction in rats with chronic obstructive pulmonary disease

Abstract

Background: Bufei Jianpi granules has been confirmed effective in improving pulmonary function, alleviating acute exacerbations, improving six-minute walk distance and quality of life, and benefited in 12-month follow-up in chronic obstructive pulmonary disease (COPD) patients with syndrome of lung-spleen qi deficiency. Skeletal muscle dysfunction (SMD), an important extrapulmonary complication, occurs in the very initiation of COPD and is closely related to morbidity and mortality. To evaluate the efficacy of Bufei Jianpi granules on SMD, we observed skeletal muscular function and histomorphology, mitochondrial morphormetry and proteins in COPD rats induced by cigarette-smoke and Klebsiella pneumoniae. Methods: Seventy-two Sprague-Dawley rats were randomized into Control + Saline, Control + Bufei Jianpi, Control + Aminophylline, COPD + Saline, COPD + Bufei Jianpi and COPD + Aminophylline groups. From week 9 to 20, rats were administrated intragastricly by normal saline, Bufei Jianpi granules and aminophylline, respectively. Muscular tension and fatigue index of intercostal muscle, quadriceps, biceps and soleus were detected by using electrophysiological technology. Pathological and ultrastructural changes and expressions of mitochondrial Bcl-2 nineteen-kilodalton interacting protein 3 (Bnip3) and cytoplasm cytochrome C (Cyto C) in the four skeletal muscles were observed by using optical and electron microscope and western blotting. Results: There was no statistical difference among the control rats treated with saline, Bufei Jianpi granules or aminophylline in above-mentioned parameters. Muscular tension, mitochondria volume density (Vv) and compared membrane surface (δm) of the four muscles were significantly lower in COPD+Saline group compared to Control+Saline group, while fatigue index, mitochondria surface area (δ), Bnip3 and Cyto C were higher (P<0.05). COPD rats showed more morphological changes in muscle tissues than controls, such as atrophy, degeneration, necrosis and matrix hyperplasia. Utrastructurally, mitochondria populations decreased significantly in the four muscles, and were shrunken and even cavitation changed. The up-mentioned parameters were improved in Bufei Jianpi group (P<0.05) in the four muscles. Conclusions: Bufei Jianpi granules can improve skeletal muscle function via improving mitochondria population and function, reducing apoptotic factors such as Bnip3 and Cyto C, and is more effective than aminophylline.