Mechanstic Investigation On Glucose Induced HK-2 Cell And DN Db/db Mice Of ALA/LA

Objectives:(1)To observe the protective effect of essential fatty acid(a-linolenic acids,ALA/linoleic acid,LA)on high glucose induced HK-2 cells and to explore the mechanisms in vitro.(2)To observe the various biological effects of ALA/LA on diabetic nephropathy(DN)db/db mice and to clarify the possible mechanisms of ALA/LA on DN db/db mice in vivo.(3)Through prevention of ALA/LA in vitro and in vivo,to observe the effects of ALA/LA on improving renal inflammatory level,oxidative stress and renal tubule fibrosis on DN db/db mice,in order to provide theoretical evidence and treatments of DN.Methods:(1)Establish the glucose injury model of HK-2 cell and the Diabetic Nephropathy injury model of db/db mouse,induced by high glucose.(2)Observe the biological effect of ALA/LA on glucose injury HK-2 cell and DN db/db mice with biochemistry methods,cytobiology methods,molecular biology methods and pathophysiology methods.Results:(1)Compared to the glucose injury model group,ALA/LA had strenghened the ability of HK-2 cell to absorb glucose(p<0.05)and then decreased the level of cytokines,oxidative stress-mediated injury and cell apoptosis.(2)Compared to the glucose injury model group,ALA/LA also decreased the protein and mRNA expression of TGF-Pi,p-p38(p38)in the intervention group.(3)After ALA/LA intervention,fasting plasma glucose,renal function,inflammation factors,the level of oxidative stress and the degree renal pathological morphology damage of db/db mice were lower in the intervention group(p<0.05).(4)Intervention of ALA/LA decreased the protein and mRNA expression of TGF-?1 p-p38(p38),p-ERK(ERK)and COL? in kidney of db/db mice(p<0.05).Conclusion:(1)ALA/LA improved recovery from the injury of HK-2 induced by high glucose,cytokines and oxidative stress.It also can inhibit gene and protein expression of p3 8,reduce the activity of TGF-?1 and then slow down the fibrosis progress of kidney.(2)ALA/LA has good antioxidant,anti-inflammatory capacity in vivo.It inhibited the transduction action of p38 and ERK,reduced the activity of TGF-?1,COL?and ameliorate kidney fibrosis of DN db/db mice.The use of ALA/LA might provide research foundation of clinical intervenrtions for DN.