| Renal insterstitial fibrosis is the final developing results of all chronic renal disease. Regardless of various kinds of primarily renal glomerular diseaes or diabetes and nephric duct, renal fibrosis process participate in renal fuction loss closely.These diseaes can cause the infiltration of renal tubular epithelial cell and myofibroblast concentrated,as well as incresed generation and decreased degradation of extracellular matrix in the presence of some fibrosis-urgeing factor.Finally,Renal inster-stitial fibrosis is produced and renal fuction is damaged seriously.Renal glomerular diseaes originated from various kinds of causes are often followed by tubulus interstitial damage.The existence or not and degree of severity of tubulus interstitial pathological changes determine the prognosis of renal diseaes.Therefore, how to avoid renal tubule insterstitial fibrosis caused by various kinds of agent has great clinical significance.Radix Salviae Miltiorrhiae has the function of promoting blood flow and removing blood stasis,improving microcirculation,inhibiting platelet aggregation,lowering blood lipid and blood consistency,eliminating oxygen free radical,reliefing small blood vessel spasm,improving oxygen deficiency,and so on..At present,research on heart and hepatic fibrosis is more about anti-fibrosis effection of salvia miltiorrhiza.But the research on the influence of salvia miltiorrhiza on renal insterstitial fibrosisis is less.In our experiment,we observed the protecting effection of salvia miltiorrhiza on renal insterstitial fibrosisis through the construction of unilateral ureteral occlusion model.Theses will provide theory basis for the application of salvia miltiorrhiza on the treatment of renal insterstitial fibrosisis.Objective:To investigate the protective effects and the mechanism of Radix Salviae Miltiorrhiae,a model of Renal Interstitial Fibrosis in Obstructive Nephropathy in Rats was set up.Methods:Thirty-two adult male wistar rats(weighing 200-220g) were randomly grouped into four groups:(1) normally group(2) sham group(3) unilateral ureteral obstruction model group(4) Radix Salviae Miltiorrhiae-treated unilateral ureteral obstruction group.Rats of normal group were not operated,Sham group was only opened its abdomen and liberated its left ureter,which was not subjected to ligation and shearing.The rats in UUO group and Radix Salviae Miltiorrhiae-treated group were subjected to left ureter ligation and shearing.The rats in the 1,2,3 group were received Sodium Chloride by stomach daily one time in the dosage of 2ml since the second day after operation.The rats in the treatment group were received Radix Salviae Miltiorrhiae daily one time in the dosage of 30mg/Kg,which is dissolved in 2ml Sodium Chloride.The 24h urine volume of rats was accurately collected before sacrifice at the end of 2 weeks.At the end of 2 weeks,rats was sacrificed and blood was getted from heart and put in common test tube.Then,the serum was taken and kept in the condition of -70℃for the biochemical indicator detection;After sacrificed,left kidneys were taken out and imbedded by paraffin,then,cut into sections of 2um,which was stained with PAS.The plasma concentrations of creatinine and urea and 24-hour urine protein were measured for the assessment of renal dysfunction and injury;The p27 and CTGF expressions were assessed by immunohischemistry for observing the state of tissue fibrosis and the anti-fibrosis ability of Radix Salviae Miltiorrhiae.Below light microscope,histomorphology change was observed. Statistical analysis:Data was presented as Mean±SD,statistical analysis was performed using one-way ANOVA,P value＜0.05 or P value＜0.01 was considered significantly.Results:1,The value of BUN,Scr,24-UP in model control group increases obviously,which,Compared with normal group and sham group,reach statistical significance (P＜0.05).Compared with model group,the value of BUN,Scr,24-UP in treatment group all decreases obviously,which reach statistical significance(P＜0.05).2,general change:The appearance of bilateral kidney of rats in normal group and sham group is normal,which looks like lima bean in size.The size of left kidney in model group and Radix Salviae Miltiorrhiae-treated group is 316mm×118mm×117mm averagely;the kidney of rats in these two groups swells obviously;its paries is thinningz and transparent partly;it is clearly evident that there is hydrops inside.When the kidney is dissected,Fluidify looks clearing and bright; renal parenchyma is thinningz obviously and its thickness is less than 1mm;The kidney is pyelectasia,nipple at renal calices is compressed,nipple at fomix flattens and part of it is foveation,nipple is ischemic and atrophys,severely,pyramid deprivates.3,Result of renal Pathological staining:both kidneys of rats in normal group and sham group has no obvious Pathological changes.Size and shape of renal glomerulus of rats in model group is normal basicly;structure of nephric tubule is destroyed seriously,part of tubulus cellula epithelialis falls off,basal membrane is outcrop,Lumen expands significantly,interstitial substance is diffuse fibrosis and inflammatory cells infiltrated.Tubular ectasia in treatment group lessens obviously,relative area of interstitium fibrous tissue diminishs.4,immunohischemistry staining semiquantitative analysis:in normal and sham group,there is no or extremely slight CTGF which expresses in nephric tubulus cellula epithelialis endochylema;in model group,the express of CTGF increases obviously in nephric tubulus cellula epithelialis and interstitial cell, which,compared with sham and normal group,has statistical difference(P＜0.05).Compared with model group,the express of CTGF in Radix Salviae Miltiorrhiae-treated group decreases obviously,which has statistical significance(P＜0.05).The express of p27 in normal and sham group is less in Renal tubular epithelial cell nuclear or caryoplasm.The express of p27 in model group increases manifestly in Renal tubular epithelial cell nuclear or caryoplasm,which,compared with sham group,reaches statistical significance(P＜0.05).Compared with model group,the express of p27 in Radix Salviae Miltiorrhiae-treated group decreases,which has statistical significance(P＜0.05).Conclusions:These findings indicate that Radix Salviae Miltiorrhiae has protective effects on Renal Interstitial Fibrosis in Obstructive Nephropathy in Rats;The mechanism may be improving microcirculation and decreasing the express of CTGF and p27 and inhibiting abnormal hypertrophia of kidney cells and reducing synthesis of Extracellular matrix;It is effective to influence kidney cells growth through intervening the cell cycle regulation mechanism in the early stage,which can delay the advancement of early obstructive nephropathy. |
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