Sesquiterpene Lactones Improve Insulin Resistance In Diabetic Mice And Kidney Damage Of Early Relief

Background:Diabetic nephropathy (DN) is a common complication of diabetes. In recent years the incidence of type2diabetes which is characterized as insulin resistance (IR) has grown up. DN is considered as a chronic inflammatory process. Recent studies have confirmed that inflammatory cytokines promotes insulin resistance. The exact mechanism needs to be studied, and it provides a new insight for the new drugs. Parthenolide has been found PTN not only has strong anti-tumor ability but also can inhibit inflammation. The mechanism may be related with inhibiting NF-κ B. The PTN’s exact effects on insulin resistance and chronic inflammation are still remained for further study.Objective:To evaluate the therapeutic effect and mechanism of treatment with Parthenolide on chronic inflammation and insulin resistance in diabetic nephropathy.Methods:The experimental group (42C57BKS db/db mice) and the control group (15db/m mice) had been fed since8weeks old. During past several weeks the experimental group was given intraperitoneal injections (qod) of PTN1. Omg/kg and weighed the body weight before each injection. In8,12,16weeks we took24hours’urine from the mice which would be put to death next day. After anesthesia we took off a eyeball, got the blood, made a perfusion into heart with ice saline and got both of kidneys and parts of liver. Tests had been made on albumin, creatinine, glucose, lipids, insulin (radioimmunoassay), MCP-1, IL-6(ELISA) in serum and albumin, creatinine in urine. And we also did the semi-quantitive analysis of tissue MCP-1and NF-κB levels by immunohistochemistry method.Results:1, The level of blood glucose, serum insulin, lipids, and urinary albumin in db/db mice is significantly higher than db/m mice (p<0.05), and gradually increased and maintained at a high level between8and16weeks.2, The level of HOMA-IR in Db/db+PTN group is significantly lower than the control group (p<0.05); and the extent of fatty liver (HE staining) and expansion of glomerular mesangial matrix (PAS staining) are significantly improved. And in16weeks the level of TC in Db/db+PTN group is significantly lower than the control group, but TG showed no such difference.3, Immunohistochemistry analysis revealed that in12weeks glomerular NF-κ B, MCP-1of Db/db+PTN group markedly reduced(p<0.05). But there was no significant difference in in16weeks.4, The level of serum MCP-1, IL-6in Db/db+PTN group is significantly lower than the control group in12weeks (p<0.05);but it seems no significant difference in16weeks.Conclusion:1, The db/db mice is a successful model of type2diabetic nephropathy.2, PTN can improve the lipid metabolism, reduce the expansion of mesangial matrix, and delay the DN pathological progress.3, PTN can reduce the expression of MCP-1and IL-6in serum and glomerular as specific antagonist on NF-κ b. Treatment with PTN on the experimental group improved the insulin resistance, which may be related with the inhibition of NF-κ b.