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Experimental Study On Ang â…¡-AT1R-CTGF Pathway To Explore How Qian Yang Yu Yin Particles Improve Renal Damage In Hypertension

Posted on:2015-09-17Degree:MasterType:Thesis
Country:ChinaCandidate:X T WangFull Text:PDF
GTID:2284330434454945Subject:Traditional Chinese Internal Medicine
Abstract/Summary:PDF Full Text Request
Background:Long-term high blood pressure can cause severe renal fibrosis,causing kidney damage.In dialysis patients our new imported in2011,about9.9%of the primary disease is high blood pressure and kidney damage.Serious threat to the the safety and quality of life of life of our people.QYYY particles is Professor Fang Zhuyuan inherit Chinese medicine practitioners Mr. Tang Shuhua academic experience,Combine his clinical practice,basis clearing liver-fire,Tonifying Kidney Activating Blood Featured drugs made.Has now been declared a Jiangsu Provincial Hospital hospital preparations.Pre-clinical studies have shown that QYYY particles hypertensive patients with renal impairment have better antihypertensive effect.And reduce urinary protein,improve kidney function, Significantly improve the quality of life of patients.However, the specific mechanism of action has not been fully elucidated.Angâ…¡-ATIR-CTGF pathway is activated in hypertensive renal damage,and promote kidney damage.Play an important role in the pathogenesis of hypertensive renal damage.RAS activation involved in a variety of kidney disease,blocking the RAS will slow the progression of glomerular sclerosis and interstitial fibrosis.CTGF as downstream regulatory factors involved in Angâ…¡ glomerular basement membrane thickening between the pathogenesis of mesangial expansion and proliferation of interstitial fibrosis and tubular.CTGF is present in many human tissues and fluids,in which the content is up to the kidneys.It can produce a variety of biological effects,including promotion of cell growth, angiogenesis,cell adhesion,apoptosis fibrosis,synthesis of extracellular matrix and vascular damage and renal disease,and can enhance the positive feedback of the activity of Angâ…¡.In this paper,hypertensive renal damage model by SHR rats,Using biochemical methods, Elisa,Western Blot, real time PCR and other methods,Interference effects QYYY particles of hypertensive renal damage,And further study its effects on Angâ…¡-AT1R-CTGF pathway.Research:Part one the theoretical study1Hypertensive renal damage in medical research2Hypertensive renal damage in modern medical research Part two the experimental study1.QYYY particle impact damage in rat model of blood pressure and urinary m-ALB, urinary NAG of hypertensive renal2.QYYY particle impact damage and fibrosis in a rat model of renal pathology of hypertensive renal 3.QYYY particle impact model of renal tissue damage Pro,Ald,Angâ…¡,ACE,AT1R of hypertensive renal4.QYYY particle impact damage in rat model of renal tissue CTGF and CTGF mRNA in renal hypertensionMethology:Picking randomly1232week-old male SHR rats were divided into four groups:model group(SHR),QYYY group(SHR+Q),benazepril group (SHR+B) and QYYY+benazepril group (SHR+Q+B).Another eight age, sex matched WKY rats normal control group.SHR+Q, SHR+B and SHR+Q+B group respectively and QYYY particle suspension5g/kg/d,benazepril suspension1.67mg/kg/d,QYYY particle suspension5g/kg/d+benazepril suspensionl.67mg/kg/d gavage.Normal group and model group were not administered.Given the same amount of distilled water.Five groups were given a normal diet.Gavage period of8weeks.Before the experiment and after the experiment using non-invasive method to measure rat tail vein blood pressure measurement.After8weeks of administration, using rat metabolic cages in groups of rats were loaded, then take a24-hour urine of rats in each group, using automatic biochemical analyzer and radioimmunoassay of rat urinary m-ALB and urinary NAG levels.HE staining staining observation of renal pathology.Masson staining renal fibrosis.Elisa assay kidney tissue Pro, Ald, Angâ…¡ levels; RT-PCR assay of CTGF mRNA levels; ACE, AT1R protein expression in renal tissue was detected by Western Blot.Results:1.Before the experiment,SHR blood pressure(systolic,diastolic) in each group were significantly higher than in WKY2.Blood test results:After8weeks of administration,QYYY each treatment group compared with the model group decreased blood pressure (P<0.01),SHR+Q+B group blood pressure was significantly lower than the SHR+Q group and SHR+B group(P<0.01or P<0.05).3.Urine Test Results:Compared with the WKY group, SHR urinary m-ALB, urinary NAG increased significantly (P<0.01); compared with SHR group, SHR+Q group, SHR+B group and SHR+Q+B urinary m-ALB, decreased urinary NAG (P<0.01or P<0.05), which SHR+Q+B group is particularly significant magnitude lower (P<0.01or P<0.05).4.Renal pathology:Compared with WKY groups, SHR group showed glomerular fibrosis, interstitial fibrosis, tubular chamber dilatation, edema, renal tubular epithelial cells, a small amount of transparency in the lumen tube, SHR+Q group, these lesions SHR+B group and SHR+Q+B group compared with SHR group relief.5.Fibrosis Index:Compared with WKY, SHR was significantly higher fibrosis index (P<0.01); Compared with SHR, SHR+Q, SHR+B can be significantly reduced SHR renal fibrosis index (P<0.01), The SHR+Q+B lower than the previous two SHR renal fibrosis index is particularly significant (P<0.01)6.Renal tissue Pro, Ald, Angâ…¡ test results:. SHR group Pro, Ald, Angâ…¡ were significantly higher than WKY group (P<0.01), SHR+Q group, SHR+B group and SHR+Q+B group Ald, Angâ…¡ were significantly lower than SHR group, which SHR+Q+B group is particularly significant magnitude lower (P<0.01or P<0.05).7.Renal tissue ACE, AT1R, CTGF protein detection:compared with WKY, SHR group ACE, AT1R, CTGF protein expression was significantly increased (P<0.01); compared with SHR, SHR+Q group, SHR+B group and SHR+Q+B on renal tissue ACE, AT1R, CTGF protein expression was significantly decreased (P<0.01); SHR+Q+B inhibition in renal tissue ACE, AT1R, CTGF protein expression level than SHR+Q group and SHR+B group (P<0.01or P <0.05)Conclusion:1. Qian Yang Yu Yin particles can significantly reduce blood pressure of SHR rats.2. Qian Yang Yu Yin particles can reduce the SHR urinary m-ALB, urinary NAG excretion, inhibit the role of kidney damage; Western drug union better.3. Qian Yang Yu Yin mechanism of action by acting on the particles is an effective target for Angâ…¡-AT1R-CTGF pathway, improving primary hypertension caused by changes in renal structure and function.
Keywords/Search Tags:Angâ…¡, AT1R, CTGF, hypertensive renal damage, Qian Yang Yu Yin particles
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