Yijing Decoction regulates MMPs/TIMPs-related molecules to antagonize high glucose-induced basement membrane damage in iBRB model

AIM: To investigate the mechanism by which Yijing Decoction antagonist high glucose-induced damage to the basement membrane(BM)in an in vitro inner blood-retinal barrier(iBRB)model.METHODS:Rat retinal microvascular pericytes(RMPs)and endothelial cells(ECs)were isolated and cultured to establish an in vitro iBRB model. The cells were randomly divided into four groups: low glucose group(LG), high glucose group(HG), minocycline group(MG)and Yijing Decoction group(YG). The LG group received 25 mmol/L glucose, the HG group received 60 mmol/L glucose, the MG group received 60 mmol/L glucose + 10 μg/mL minocycline, and the YG group received 60 mmol/L glucose + 10% Yijing Decoction-containing serum. Incubation for each group were terminated after intervention for 12 h. Next, the Western blot analysis was performed to assess the protein expression of BM-related proteins, including collagen Ⅳ(CⅣ)and laminin(LN), as well as matrix metalloproteinase(MMPs)/tissue inhibitor of matrix metalloproteinases(TIMPs)such as MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2.RESULTS:Compared to the LG group, the protein expressions of CⅣ increased in the HG, MG, and YG groups, as did LN in the HG and MG groups(all P<0.05). Both Yijing Decoction and minocycline effectively inhibited the elevated expression of CⅣ and LN induced by high glucose, and the difference between the YG, MG, and HG groups was statistically significant(all P<0.05). Futhermore, compared to the LG group, the protein expressions of MMP-2, MMP-3, and MMP-9 increased in the HG, MG, and YG groups(all P<0.05). Yijing Decoction specifically attenuated the high glucose-induced increase in MMP-2, MMP-3 and MMP-9 protein expression, and there were statistically significant differences between the YG and HG group(all P<0.05). No significant difference were observed in the expressions of TIMP-1 and TIMP-2 among the LG, HG, MG, and YG groups(all P>0.05).CONCLUSION:Yijing Decoction can potentially intervene in DR by modulating the protein expression of MMP-2, MMP-3, MMP-9, CⅣ, and LN, suppressing high glucose-induced BM remodeling, and mitigating damage to iBRB.