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Expression of vWF and PAI-1in the Kidney of Diabetic Rats and Effect of Danhong Injection and Metformin

Author: GaoZuo
Tutor: WangZhanJian
School: Hebei Medical University
Course: Internal Medicine
Keywords: Diabetic nephropathy vWF PAI-1 Danhong injection metformin
CLC: R587.2
Type: Master's thesis
Year: 2014
Downloads: 7
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Abstract


Objective: Diabetes mellitus is a kind of whole body chronic metabolicdisease, The incidence of which is increasing year and year. Diabeticnephropathy(DN) is the most common and severe microvascular complicationof diabetic mellitus and has become a major cause of end-stage renal failure. Itis multi-factors that attribute to occurrence and development of DN. DN isclosely related to multiple factors such as the disorder of glucose metabolism,hemodynamics, cytokine, oxidative stress, inflammatory response and hemor-heology. The changes of hemorheology are the main reason ofmicrocirculation disturbance with diabetes, which play an important role in thedevelopment of DN. Von Willebrand factor(VWF), Plasminogen ActivatorInhibitor-1(PAI-1) can reflect the changes of coagulation and fibrinolysisfunction, which are involved in the occurrence and development of DN. vWFis an important maker of endothelial injury. Rising level of vWF promotes thehypercoagulable state. PAI-1is the main regulator of the fibrinolytic system,which can inhibit plasminogen activation. Danhong injection has markedactions of promoting blood circulation to remove blood stasis. Metformin is asafe and effective hypoglycemic drug which is widely used for the treatmentof diabetes. Meanwhile metformin can regulate blood lipids, reduce plateletaggregation and improve blood rheology. Danhong injection and metforminmay prevent the progression of DN, but the concrete mechanism needs furtherstudy. In this study, the level of serum vWF and expression of vWF and PAI-1in the kidney of diabetic rats before and after the intervention of Danhonginjection and metformin were detected. The pathogenesis of DN andrenoprotective effects of Danhong injection and metformin remain to befurther studied.Methods:48male SD rats were divided into two groups randomly:10 normal control rats(group A) and38test rats. All the test rats were establishedan animal model of diabetes by a single intraperitoneal injection ofstreptozotocin(STZ,55mg/kg). After72hours, the rats whose blood glucoselevel were higher than16.7mmol/L in the subsequent3days were regarded asdiabetes. The diabetic rats were randomly divided into following groups:14diabetic rats(group B),12Danhong intervention rats(group C) and12metformin intervention rats (group D). Danhong injection (2.0ml/kg.d) wasgiven by intraperitoneal injection to group C. Metformin (300mg/kg.d) wasadministrated by a stomach tube in group D. The same amount of saline wasgiven by intraperitoneal injection to group A and group B. The experimentlasted for eight weeks. At the end of eight weeks, blood, urine and renal tissuesamples were collected in four groups of rats. Then blood glucose (BG), totalcholesterol(TC), triglyceride (TG), low density lipoprotein cholesterol(LDL-C), serum creatinine (Scr), blood urea nitrogen(BUN),24h urinaryalbumin were tested. Serum vWF was detected by Enzyme-linkedimmunoassay(ELISA). We used HE staining to observe the renal pathologicalchanges under optical microscope. Expression of vWF in renal tissue wasmeasured by immunohistochemistry. The images were analyzed by imageanalysis system. Renal vWF, PAI-1mRNA expression were measured byreal-time fluorescent quantitative PCR. The data were analyzed by SPSS16.0system, then adopted one-way ANOVE and non-parametric test, and P<0.05was considered to have statistical significance.Results:1After eight weeks, compared with group A, the BG, TC, TG, LDL-C, Scr,BUN,24h urinary albumin, Kidney hypertrophy index were significantlyhigher in group B(P<0.01). After treated by Danhong injection and metformin,TC, TG, LDL-C, Scr, BUN,24h urinary albumin, Kidney hypertrophy indexwere obviously reduced((P<0.05). The BG of group D was significantly lowerthan that of group B(P<0.01).2Serum vWF: The concentrations of Serum vWF in group B was significantlyhigher than that of group A(P<0.01). It was lessened in group C and D (P<0.01). The difference was statistically significant.3The morphological examination: There were obvious pathological changesin kidneys of diabetic rats. The average sectional area of glomerulus in groupB rats was increased. There were a slight mesangial cell proliferation. Thekidney showed some renal tubular epithelial cells atrophy and the tubularrevealed dilatation. There was a mitigated pathological change in renal tissuesin group C and group D.4The protein expression of vWF in renal tissue: Immunohistochemicalanalysis showed that the expression of vWF in group B was significantlyincreased than that in group A(P<0.01). The expression of vWF in group Cand group D was lower than that in group B(P<0.01), but was much higherthan of group A.5Real-time fluorescent quantitative PCR shows: Compared with group A,vWF, PAI-1mRNA were increased significantly(P<0.01). The expression ofvWF, PAI-1mRNA in group C and group D were lower than that in groupB(P<0.05). The relative expression of vWFmRNA in group B, group C andgroup D was5.09times,3.45times and3.19times respectively as high as ingroup A. The relative expression of PAI-1mRNA in group B, group C andgroup D was4.31times,2.70times and2.98times respectively comparedwith group A.Conclusion:1The serum vWF level and the expression of vWF, PAI-1in the kidney oftype1diabetie rats were increased significantly, which may be involved in theoccurence and development of diabetic nephropathy.2Danhong injection and metformin have renoprotective effect on diabeticnephropathy by regulating the levels of serum lipids, reducing the level ofalbuminuria and suppressing vWF, PAI-1expression.

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CLC: > Medicine, health > Internal Medicine > Endocrine diseases and metabolic diseases > Islet disease > Diabetic coma and other complications
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