Dissertation
Dissertation > Medicine, health > Chinese Medicine > Of Pharmacy > Pharmacology > Chinese medicine Experimental Pharmacology

AGEs Aggravate Diabetic Nephropathy and Loganin,Morroniside Intervention Mechanism Study

Author LiuBin
Tutor XuHuiQin
School Nanjing University of Traditional Chinese Medicine
Course Pharmacology
Keywords AGEs diabetic nephropathy urine protein serum urea nitrogen RAGEmRNA RAGELoganin Morroniside RAGE
CLC R285.5
Type Master's thesis
Year 2013
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Objective:To establish AGEs aggravate STZ induced diabetic nephropathy in a mouse model, in this kind of diabetic nephropathy model, system development mechanism. Basec food AGEs can cause kidney damage, around the AGEs-RAGE pathway, the establishment of a new model of diabetic nephropathy AGEs path. Methods:male C57BL/6J mice were6weeks o: age, and the establishment of a blank control group of AGEs group, STZ group and STZ+AGEs group. STZ group and STZ+AGEs group on the first day, four days100mg/kg dose according to body weight by intraperitoneal injection of STZ, the other two groups were injected with equivalent citric acid-sodium citrate buffer, measured8days in mice fasting glucose, The selected blood sugar value is greater than15mmol/L mice as diabetic mice modeling. AGEs group, STZ+AGEs group of mice fed high AGEs diet, the control group and the STZ mice tc ordinary AIN-93G diet, these groups of10.12weekend mice eyeballs blood separation pancreas, kidney, to a solution of formalin fixed, after weighing the part of the slice to glutaraldehyde fixed the remaining kidney to-80℃saved determination of the following indicators:(1) every fou(?) weeks, blood glucose, body weight, food intake, water intake, urine output was measured.(2) renal indicators:urinary protein, urine creatinine, serum urea nitrogen (3), pancreas, kidney pathological examination (including optical microscopy, electron microscopy).(4) RT-PCR detection the renal cortex RAGEmRNA of expression, Western Blot renal cortical RAGE protein expression. Results:of STZ+of AGEs mice food intake, water intake, urine output, blood glucose increased significantly (P<0.01), insulin levels (P<0.01), renal indicators:urine protein, urine creatinine, blood urea nitrogen increased (P<0.05, P<0.01), serum, kidney AGEs levels increased (P<0.01), renal cortex RAGEmRNA, RAGE protein expression, pathological results showed significant diabetic nephropathy, which STZ+AGEs mice STZ and AGEs group was significantly higher than the degree of kidney damage, AGEs can aggravate diabetic kidney damage. Conclusion:In this experiment, STZ caused hyperglycemia in mice, successfully causing a diabetic nephropathy model diet supplemented with high AGEs, and AGEs can accelerate diabetic nephropathy, shorten modeling time, a better simulation of human diabetic nephropathy disease process, such diabetic nephropathy model for the establishment of an animal model of non-obese diabetic nephropathy has important practical significance. PART Ⅱ Mechanism of the effect on The AGEs aggravate STZ induced diabetic nephropathy in mice model by the Loganin and MorronisideObjective:AGEs aggravate STZ induced diabetic mice nephropathy model based on blood glucose in diabetic mice," More food, More water, More urine, and less weight ", the relevant indicators of renal function, renal pathological changes, AGEs and its receptor RAGE gene and protein levels The other aspects detection depth study of the mechanism of action for the treatment of diabetic nephropathy Loganin Morroniside. Methods: Take6weeks old male C57BL/6J mice, adaptive feeding, respectively, on the first day, the first f our days in accordance with a dose of100mg/kg body weight by intraperitoneal injection of STZ solution, and the remaining two groups injected with equivalent citric acid-citric acid sodium ci trate buffer, the first eight days of fasting blood glucose measurements mouse, select the glucose values greater than15mmol/Lmice as a successful model of diabetes in mice. The successful m odeling according to blood glucose in mice divided into model group, aminoguanidine group (0.1g/kg), metformin group (0.2g/kg), captopril group (0.02g/kg), low-dose group loganin (0.02g/k g), loganin high dose group (0.1g/kg), morroniside low dose group (0.02g/kg), morroniside high dose group (0.1g/kg), separate the normal group, n=10, in addition to the normal group than in mice fed with normal diet the rest of the group are outside the high AGEs diet. Each group were administered doses of the drug for12weeks, in mice of the model group and blank control group distilled water. In12weeks, the mice eyeballs blood, the pancreas, kidney was separated, weighed to10%formalin solution for fixation, part of the slice to2.5%glutaraldehyde fixed, and the remaining kidney to-80℃save the determination indicators are as follows:(1) every four weeks Determination of blood glucose, body weight, food intake, water intake, urine output.(2) renal indicators:urinary protein, urine creatinine, serum urea nitrogen (3), pancreas, kidney pathological examination (including optical microscopy, electron microscopy).(4) RT-PCR detection the renal cortex RAGEmRNA of expression, Western Blot renal cortical RAGE protein expression. Results:The model mice appeared hyperglycemia, polydipsia, polyphagia, polyuria, proteinuria and kidney damage and other symptoms caused by diabetic nephropathy model successfully. Compared with the model group Loganin Morroniside can significantly reduce diabetic nephropathy in mice blood glucose (P<0.05, P<0.01), improved " More food, More water, More urine, and less weight " symptoms (P<0.05, P<0.01) increase insulin secretion (P <0.05, P<0.01), lower urinary protein, urine creatinine, blood urea nitrogen (P<0.05, P<0.01), to alleviate the pathological changes of the pancreas, kidney disease, lower serum, kidney AGEs level (P<0.05, P<0.01), lowered renal cortical RAGE protein expression of RAGE. Conclusion: Loganin Morroniside can significantly lower blood glucose in diabetic nephropathy and to improve the symptoms of diabetes and promote insulin secretion, reduce proteinuria, protecting the kidneys of diabetic mice, and its mechanism of action may promote islet cell proliferation, correct sugar and metabolism disorders, reduce serum and kidneys AGEs content down the renal cortex RAGEmRNA, RAGE protein expression.

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