ABSTRACT
Objective To observe the intervention effect of salvianolic acid A ( SAA) on retinopathy of Zucker diabetic fatty ( ZDF ) rats and explore the possible action mechanism of SAA to prevent and treat diabetic retinopathy ( DR) . Methods Thirty-two 7-8-week old ZDF rats were taken and fed with Purina rat chow for 4 weeks. The ZDF rats were equally divided by the blood glucose into model group, 0. 5 mg/kg SAA group, 1. 0 mg/kg SAA group and metformin ( Met) group. 8 Zucker lean ( ZL) rats were taken as control group. After 12-week administration, incidence of cataracts and retinal pathology was observed, and levels of GLU, TC and HbA1c in blood, transferrin ( TRF) and retinol binding protein ( RBP) in urine and levels of interleukin-1 ( IL-1 ) , interleukin-6 ( IL-6 ) , oxidized low density lipoprotein ( ox-LDL), malondialdehyde (MDA) and lipoprotein related phospholipase A2 (Lp-PLA2) activity in serum were measured. Results In the model group, GLU, TC, HbA1c , diabetic cataract incidence rate, retinal basement thickening and microangiopathy appeared in most of the rats. The levels of TRF and RBP in urine and levels of IL-1, IL-6, ox-LDL, MDA in serum were significantly increased, and Lp-PLA2 activity was also significantly increased. After SAA administration, the morbidity rate of cataract was reduced, and retinal pathological changes were improved in different degrees. The levels of TRF, RBP, IL-1, IL-6, ox-LDL, MDA and Lp-PLA2 activity was decreased. Conclusions SAA can slow down the process of diabetic retinopathy in ZDF rats and reduce the incidence of cataract. The mechanisms of action may be related to inhibition of chronic inflammation, prevention of lipid peroxidation and reduction of Lp-PLA2 activity.
ABSTRACT
Objective To observe the intervention effect of salvianolic acid A ( SAA) on retinopathy of Zucker diabetic fatty ( ZDF ) rats and explore the possible action mechanism of SAA to prevent and treat diabetic retinopathy ( DR) . Methods Thirty-two 7-8-week old ZDF rats were taken and fed with Purina rat chow for 4 weeks. The ZDF rats were equally divided by the blood glucose into model group, 0. 5 mg/kg SAA group, 1. 0 mg/kg SAA group and metformin ( Met) group. 8 Zucker lean ( ZL) rats were taken as control group. After 12-week administration, incidence of cataracts and retinal pathology was observed, and levels of GLU, TC and HbA1c in blood, transferrin ( TRF) and retinol binding protein ( RBP) in urine and levels of interleukin-1 ( IL-1 ) , interleukin-6 ( IL-6 ) , oxidized low density lipoprotein ( ox-LDL), malondialdehyde (MDA) and lipoprotein related phospholipase A2 (Lp-PLA2) activity in serum were measured. Results In the model group, GLU, TC, HbA1c , diabetic cataract incidence rate, retinal basement thickening and microangiopathy appeared in most of the rats. The levels of TRF and RBP in urine and levels of IL-1, IL-6, ox-LDL, MDA in serum were significantly increased, and Lp-PLA2 activity was also significantly increased. After SAA administration, the morbidity rate of cataract was reduced, and retinal pathological changes were improved in different degrees. The levels of TRF, RBP, IL-1, IL-6, ox-LDL, MDA and Lp-PLA2 activity was decreased. Conclusions SAA can slow down the process of diabetic retinopathy in ZDF rats and reduce the incidence of cataract. The mechanisms of action may be related to inhibition of chronic inflammation, prevention of lipid peroxidation and reduction of Lp-PLA2 activity.
ABSTRACT
BACKGROUND: An exogenous supplement of n-3 polyunsaturated fatty acids (PUFAs) has been reported to prevent osteoarthritis (OA) through undefined mechanisms. OBJECTIVE: This study investigated the effect of alterations in the composition of endogenous PUFAs on OA, and associations of PUFAs with mammalian target of rapamycin complex 1 (mTORC1) signalling, a critical autophagy pathway in fat-1 transgenic (TG) mice. METHODS: fat-1 TG and wild-type mice were used to create an OA model by resecting the medial meniscus. The composition of the endogenous PUFAs in mouse tissues was analysed by gas chromatography, and the incidence of OA was evaluated by micro-computed tomography (micro-CT), scanning electron microscopy and histological methods. Additionally, primary chondrocytes were isolated and cultured. The effect of exogenous and endogenous PUFAs on mTORC1 activity and autophagy in chondrocytes was assessed. RESULTS: The composition of endogenous PUFAs of TG mice was optimised both by increased n-3 PUFAs and decreased n-6 PUFAs, which significantly alleviated the articular cartilage destruction and osteophytosis in the OA model (p<0.01), decreased protein expression of matrix metalloproteinase-13 (MMP-13) and ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs) in the articular cartilage (p<0.01) and reduced chondrocyte number and loss of cartilage extracellular matrix. Both exogenous and endogenous n-3 PUFAs downregulated mTORC1 activity and promoted autophagy in articular chondrocytes. Conversely, mTORC1 pathway activation suppressed autophagy in articular chondrocytes. CONCLUSIONS: Enhancement of the synthesis of endogenous n-3 PUFAs from n-6 PUFAs can delay the incidence of OA, probably through inhibition of mTORC1, promotion of autophagy and cell survival in cartilage chondrocytes. Future investigation into the role of the endogenous n-6/n-3 PUFAs composition in OA prevention and treatment is warranted.
