| There is an increasing number of populations suffering from diabetes due to the china’s social-economy development, people’s life style changes, and decreasing physical activity and increasing number of obesity people. According to the article published in New England Medicine2010, it was estimated that the incidence of over20year old diabetes sufferer is about9.7%, for pre-diabetes the number is15.5%, and now it has been a severe public health problem. Chinese medicine plays a critical role in diabetes prevention and treatment, for example, professor Lin Lan with over40years of clinical expertise and researches in Guang’ anmen Hospital Affiliated to China Academy of Chinese Medical Sciences, created the theory of three syndromes for diabetes in Chinese medicine, including yin deficiency due to excessive heat, qi&yin deficiency, and yin&yang deficiency, which summarized the dynamic alteration laws of diabetes, benefits clinical practice of diabetes in Chinese medicine. Qingrun formula (composed of huangbai, dahuang liquid soaked, zhimu) is specialized for diabetes early stage, the principle of nourishing yin and clearing heat works well for the diabetes syndrome of yin deficiency due to excessive heat. This study mainly focus on Qingrun formula’s potential mechanism of lipid metabolism, liver inflammation, and oxidative stress, key gene mRNA expression on skeletal muscle metabolism, seeking theoretical evidence and database for clinical practice.1. Reviews:several parts will be discussed, including the relation between diabetes and insulin resistance, present research on mechanism of insulin resistance (disorder of lipid metabolism, inflammation and oxidative stress, insulin resistance in skeletal muscle), composing principle of Qingrun formula, and s modern study of single herb in the formula, and Chinese medicine treatment for diabetes.2. Experimental trials:four basic experiments are referred.2.1Qingrun formula’s effect on glucose metabolism and pancreatic pathology&morphology in experimental diabetes mice. Objective:to observe Qingrun formula’s effect on glucose metabolism and pancreatic pathology&morphology in experimental diabetes mice. Method: diabetes mice models were created by combination of streptozotocin and high sugar&lipid feeding. Experimental animals were divided into6groups, including contrast, model, Qingrun formula small, moderate, and high dosage (respective0.5,1,2g·kg-1·d-1), and Metformin groups; all groups were given medication by gastric lavage. With4weeks intervention, the mice were measured weight, fasting blood glucose, insulin level in blood, AUC, ISI, insulin resistance index, changes of pancreatic pathology&morphology in the optical microscope and electron microscope. Results:FBG was lower in Qingrun formula’s moderate&high dosage and Metformin groups than model group (P<0.05); AUC in all three Qingrun formula and Metformin groups decreased individually (P<0.05); ISI in Qingrun formula’s moderate&small dosage and Metformin groups were higher than model group, meantime, IRI is decreased (P<0.05); hepatic glycogen were increased in Qingrun formula’s moderate&small dosage and Metformin group (P<0.05); in optical microscope, pancreatic islet account decreasing was improved in Qingrun formula’s moderate&high dosage and Metformin groups, although partial islet size became smaller, occasionally larger ones is seen; in electron microscope, endocrine granule secreted by pancreatic islet (3-cell increased in all three Qingrun formula’s and Metformin groups was much more than model group. Consults:Qingrun formula has good effects on lowering blood glucose in mice, the mechanism maybe referred to insulin resistance, protection of pancreatic islet, and improvement of glucose utilization and hepatic glycogen synthesis.2.2Qingrun formula’s effect on lipid metabolism and liver pathology and morphology in experimental diabetes miceObjective:to observe Qingrun formula’s effect on lipid metabolism and liver pathology and morphology in experimental diabetes mice, and discuss the function of improving insulin resistance in lipid mechanism. Method:with4weeks intervention, the mice were taken blood test, liver tissue test, TCHO by blood automatic biochemical analyzer COD-PAP, TG test by GPO-PAP, HDL-C&LDL-C measured by elimination method; Serum free fatty acid was measured with cooper color; liver tissue pathology and morphology changes in optical microscope was observed. Results:in comparison to model group, TCHO、LDL-C of diabetes mice lowered in Qingrun formulas moderate&high dosage groups (P<0.05); HDL-C increased in all three Qingrun formula and Metformin groups (P<0.05), TG showed decreased tendency without significance; Serum free fatty acid decreased in Qingrun formula’s moderate&small dosage and Metformin groups (P<0.05); in optical microscope, liver fat deposition were improved in Qingrun formula’s moderate&high dosage and Metformin groups. Consults:Qingrun formula has good effects on lipid metabolism and inhabiting liver fat deposition in diabetes mice. Qingrun formula’s effect on lipid toxicity in diabetes mice related to the mechanism of insulin resistance.2.3Qingrun formula’s effect on liver inflammation and oxidative stress in experimental diabetes miceObjective:to observe Qingrun formula’s effect on liver inflammation and oxidative stress in experimental diabetes mice, and discuss the mechanism. Method: with4weeks intervention, liver tissue were taken out from mice, TNF-α and IL-6were measured by ELISA, MDA content and SOD activity of liver tissue were tested with colorimetry. Results:in comparison to model group, TNF-α lowered in all three Qingrun formula groups (P<0.05); IL-6of liver tissue decreased in Qingrun formula’s small&high dosage groups (P<0.05), slight decreased tendency in Qingrun formula moderate dosage without significance; MDA in liver tissue decreased in Qingrun formula’s moderate&small dosage and Metformin groups (P <0.05), meantime, SOD increased in Qingrun formula moderate&high dosage groups. Consults:Qingrun formula has good effects on lowering inflammatory factors in liver tissue by improve Oxygen free radical scavenging to decrease tissue damage. Controlling chronic inflammation and oxidative stress damage account for the mechanism of Qingrun formula in improving insulin resistance. 2.4Qingrun formula’s effects on skeletal muscle GLUT-4、INSR mRNA expression in experimental diabetes miceObjective:Qingrun formula’s effects on skeletal muscle GLUT-4、INSR mRNA expression in experimental diabetes mice, and discuss the function of insulin resistance in skeletal muscle. Method:with4weeks intervention, skeletal muscle of left posterior legs were taken out in sterile conditions to exam GLUT-4、INSR mRNA expression by PCR. Results:in comparison to model group, GLUT-4mRNA expression increased in Qingrun formula’s moderate&high dosage and Metformin groups (P<0.05), INSR mRNA expression increased without significance. Consults: Qingrun formula has a role of upgrading skeletal muscle GLUT-4mRNA expression, improving glucose utilization in skeletal muscle, which is related to the mechanism of insulin resistance in diabetes mice.Above mentioned, this study shows that Qingrun formula has good effects on lowering blood glucose, improving insulin resistance, and protecting pancreatic islet, which the functions relate to promote lipid metabolism, and decrease lipid toxicity; controlling liver chronic inflammation and decreasing oxidative stress damage to improve liver pancreatic islet insulin resistance; promoting glucose utilization in skeletal muscle to improve insulin resistance. Besides, Qingrun formula provided theoretical evidence and database for Chinese medicine application in yin deficiency due to excessive heat in three syndromes. |
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