| Type 2 diabetes mellitus is features chronic metabolic disease with deficiency of insulin secretion and/ or insulin resistance caused by ? cell dysfunction,resulting in the disorder of blood glucose and lipid metabolism,and eventually leading to pathological damage of liver,heart,kidney and other organs.Diabetic cardiomyopathy and nephropathy are serious vascular complications induced by hyperglycemia.Histostructural fibrosis is the main pathological feature of diabetic cardiomyopathy and nephropathy.Recent studies have shown that the fibrosis may be connected with the increase of extracellular matrix deposition and the acceleration of epithelial mesenchymal transformation.Reducing the fibrosis of tissue structure will slow down the development of type II diabetes.The changes of blood related indexes,insulin resistance and fibrosis related proteins in type 2 diabetes reflect the development of type 2 diabetes and its complications,which may become the targets of treatment of type 2 diabetes and its heart and kidney complications.Dendrobium officinale Kimura et Migo,a traditional Chinese medicinal material belonging to Dendrobium of Orchidaceae,which has been used in many Asian countries for thousands of years.Its reported that Dendrobium officinale has good pharmacological activity in hyperglycemia,hypoimmunity,hypertension,tumor and other diseases.Polysaccharide is the main component of Dendrobium officinale.Our previous study found that Dendrobium officinale polysaccharide has a good anti-inflammatory activity and a strong protective effect on myocardial damage caused by ischemia and diabetes mellitus though inhibiting the release of inflammatory factors.Therefore,based on the previous research results of the laboratory,the model mice of type II diabetes were used to study the effects of polysaccharide from water extract of Dendrobium officinale(DOE)on blood indexes,insulin resistance,morphological changes of heart and kidney,and related proteins of type II diabetes.The research is divided into four parts: 1)identification of the DOE,2)detection of the impact of the DOE on the blood indexes of model mice,3)The effects of DOE on the morphological changes of heart and kidney tissue of model mice analyzed by histological method,4)the changes of insulin resistance and fibrosis related protein expression of model mice analyzed by Western blotting.The polysaccharide content,monosaccharide species and content of Dendrobium officinale aqueous extract were analyzed by phenol sulfuric acid method and High Performance Liquid Chromatography method.The results showed that the polysaccharide was the main component of the DOE,the content of which was 44.83%.The polysaccharide mainly included mannose and glucose,the content of which were 28.97% and 4.60%,respectively.Mice were fed with high fat diet for 2 weeks,and then 30 mg/kg streptozotocin(STZ)was used for 5 days to induce type II diabetic model.After the establishment of the model,the mice were divided into five groups: model group,low,medium,high dose group treated with DOE and metformin positive control group,10 mice in each group.Mice in the control group and model group were given normal saline every day,and DOE were given 75 mg / kg,150 mg / kg and 300 mg / kg every day in the low,medium and high dose groups,respectively,And metformin was given 125 mg / kg every day in the metformin positive control group for 12 weeks.Body weight of mice was measured every day.Fasting blood glucose level was recorded every week during administration.The mice were euthanized,then plasma samples were collected.The heart,kidney and the liver tissues were collected and weighted.The results of blood glucose test showed that the DOE decreased the fasting blood glucose level of type ? diabetic mice.The results of automatic biochemical analyzer showed that the DOE could reduce the triglyceride(TG),total cholesterol(TC),low-density lipoprotein(LDLC)and increase the content of high-density lipoprotein(HDL-C)in the serum of model mice.The results of ELISA revealed that the DOE could reduce the serum insulin level of the model mice.HOMA-IR results showed that the DOE relieved the insulin resistance in diabetic mice.Hematoxylin-eosin staining showed obvious amelioration of cardiac injury and renal injury after administration of the DOE.Myocardial cells were arranged orderly,vacuole like lesions were reduced and no obvious inflammatory cell infiltration was found.Glomerular basement membrane thickening,glomerular hypertrophy and mesangial matrix dilation were relieved in renal tissue.Sirius red staining showed that DOE could significantly reduce lipid accumulation and collagen deposition in myocardial and renal tissues.TUNEL detection the results showed that the DOE could significantly reduce the apoptosis of cells in kidney.Western blotting analysis was performed to analysis the expression of PPAR-??p-JNK?pIRS1?TGF-?1?CTGF?Fibronectin?Akt?PI3K?Twist?Snail1?Vimentin and E-cadherin.The results showed that the DOE increased PPAR-? and p-IRS1 protein in the liver and decreased p-JNK protein in the liver,indicating that the DOE increased fatty acid oxidation and lipid transport,and reduced insulin resistance.DOE decreased the expression of TGF-?1,CTGF,fibronectin,Akt and PI3 K protein in heart and kidney,which indicated that DOE inhibited the release of fibrogenic factors and the deposition of extracellular matrix.In addition,DOE reduced the expression of twist,Snail1 and Vimentin protein in heart and kidney,and increased the expression of E-cadherin protein,indicating that DOE can effectively suppress the transformation of epithelial mesenchymal,and reduce the fibrosis of heart and kidney.In conclusion,the DOE possessed better effects on decreasing blood glucose,reducing blood lipid,improving insulin resistance,reducing organ tissue damage,reducing heart and kidney fibrosis. |
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