Effects Of Rhein On Islet Function, Inflammation And Oxidative Damage Markers In Db / Db Mice

Insulin resistance andβ-cell dysfunction are the main pathogenesis of type 2 diabetes.The results of UKPDS showed that β-cell function of newly diagnosed type 2 diabetes patients was only 50% of the normal people, and then declined at a rate of about 4.5% per year. The dysfunction of islet 3-cell is caused by many factors. It was found that insulin resistance was a chronic subclinical inflammatory process. At the same time, inflammation is also an important factor of 3-cell dysfunction in diabetic state. Related study shows, the islets of type 2 diabetes patients often present the amyloid deposition, fibrosis, and increased cell death, which are closely related with the inflammatory response, and the body’s inflammatory response starts at the same time in islet cell apoptosis or necrosis, The expression of inflammatory factors, such as:IL-1, IL-6 and TNF-α etc.,their high expression can block the biological function of insul in in the body, decrease the sensitivity of nsulin, lead to the occurrence of nsulin resistance. Another important factor contributes toβ-cell dysfunction in type 2 diabetes patients is ox i dative stress. Ox i dative stress can make the islet function of the body obstacle and lead to the occurrence and development of type 2 diabetes by inhibiting islet β-cell secretion, destructing the signal transduction pathway of insulin and prompting the apoptosis of islet β-cell, etc.The NF-κB is a kind of protein factor with a variety of multi-directional transcriptional regulation. It participates in immune regulation mediated inflammation and a variety of physiological and pathological processes of the gene transcription.While,8-OHdG is the main and the specific product of DNA oxidative stress damage, it can reflect the levels of DNA oxidative stress damage. So, this experiment choose the NF-kappa B and 8-OHdG as the markers of inf I ammation and oxidative stress damage.Rhein is a kind of monomer component, which is distributed in the polygonaceae in plants, it is a kind of anthraquinone derivatives, it can be separated and purificated from rhubarb, fleece-flower root, giant knotweed etc. which are all traditional Chinese medicine, and it has many kinds of pharmacological activities,such as:anti-tumor, anti-inf lamm atory, and diuretic, anti fibrosis, antibacterial, antioxidant and so on. This experiment choosed db/db mice as the animal mode I s, wh i ch were congenital type 2 diabetes. And the aim of the present study was to investigate the effects of rhein on the markers of insulin secretory function、inflammation and oxidative stress damage.Methods:Thirty db/db mice at 4 weeks of age were randomly allocated to two groups, and 15 mice in each group. The treatment group was gavaged with rhein(120mg/kg supplemented with 1% sodium cellulose solution) at a fixed time everyday and an aliquot of 1% sodium cellulose in the control group for 8 weeks.They were monitored with random blood glucose and body mass at a fixed time every week. After the administration, they were conducted with intraperitoneal glucose tolerance test (IPGTT), and measured the insulin I eve Is. The levels of insuli n secretion were presented by the area under curve (AUC). And by calculating the insulin area under the curve of the 0-30 min of IPGTT to assess the function of the early secretion. At the same time, immunohistochemical staining was employed to assay the level of i nsu I i n, NF-κB and 8-OHdG i n the pancreas.Results:Compared with the control group, the treatment of rhein resulted in substantially reduced blood glucose concentrations at 0,30,60 and 120 min yet markedly increased level s of insulin at 30,60 and 120 min, especially in the early phase,insulin levels increased more significantly. Meanwhil e,the i nsu li n staining of the treatment group was s i gn i f i cant I y enhanced yet the expressions of NF-κB and 8-OHdG were attenuatedConclusions:Early-phase treatment of rhein significantly improves glucose tolerance, restores early-phase insulin secretion and protects islet function;meanwhile, early-phase treatment of rhein significantly reduces the expression of the markers of inflammatory and oxidative stress damage.