The Role Of PKC-MMPs/TIMPs Signalling Road In The Mechanism Of Diabetic Nephropathy

Background: The patients of Diabetes mellitus( DM) have increased rapidly in the world.Diabetic nephropathy(DN) is one of the most serious complications of DM. Some studies showed that the deposition of extracelluar matrix is an important reason.Athough many studies about the mechanism of DN have been performed in past years,the precise mechanism of DN is not well understood. Some investigators recongnized that protein kinase C(PKC) has played an important role in the mechanism of DN.High glucose can activate PKC in mesangial cells and contribute to the deposition of extracelluar matrix of diabetic nephropathy. Some other studies suggested that high glucose changed the activity of MMPs in the messangial cells .The MMPs/TIMPs in the messangial cells is decreased under high glucose medium.However,the relationship between PKC and MMPs/TIMPs in DN is unclear.Objective: To explore the relationship between PKC and MMPs/TIMPs in human messangial cells under the high glucose medium and the kidney tissues of DN rats.To analyze the effect of PKC and MMPs/TIMPs in the developing of DN.Methods: 1 Normal human mesangial cells( NHMC ) in vitro were divided into 4 groups. control group(N, 5mmol/L), high glucose group(H,30mmol/L), PKC inhibited group (P,30mmol/L glucose plus chelery thrine chloride )and osmotic control group (O,5mmol/L glucose plus 25mmol/L mannitol). Cell proliferation was measured by MTT at 24,48or72 hours.The activity of PKC is measured by ELISA and the mRNA and protein expressions of MMP2,9 and TIMP1,2 were examined by RT-PCR and Western blot2 Wistar rats were divided at random into normal control group and diabetic nephritic model group and treatment group with the inhibition of...