| Objectives: Renal fibrosis are the characteristics of diabetic nephropathy,which is the final common pathway to end-stage renal disease.Tubulointerstitial lesions may be the key step,Myofibroblasts are a group ofsmooth-muscle-like fibroblasts and about36%of new fiber cells derived fromrenal tubular epithelial cells. Researcher have shown that tubularepithelial-myofibroblast transdif-ferentiation can occur to the renal tubularepithelial cells in Injury condition. It is of great significance to find effectivemeans to block it at home and abroad.The Chinese medicine is of advantageto multiple targets, multiple pathways,the whole concept and thedifferentiation of symptoms.It has broad prospects in clinical prevention ofDN. According to the pathogenesis of DN and clinical experience for treatingDN, Mentor professor Chen Zhiqiang invented the fundamental principle ofDN is for qi and yin deficiency,dispersing blood stasis and dredging thecollaterals, Insect drugs was composed of Leech,Earthworm,Wholeworm.Root grass medicine was composed of Radix salviae miltiorrhizae,Rhizoma Chuanxiong, Furthermore,the advantage has been demonstrated byclinical study, The study set up diabetic rat models, and be applied withsupplementing qi and nourishing yin dredging meridians,To explore the effectof the formula on DN and the possible mechanism in TEMT, interms ofILK/SMA.Methods: Forty male Sprague-Dauley rats weighted125g±23g is for ourstudy. According to the weight, the animals were randomly divided intonormal group(10rats)and HFD groups(30rats). HFD rats were feed withhigh fat and injected with streptozotocin (STZ) in the dose of30mg/kg,After72hours, we measured the tail vein blood randomly for3times. If the blood glucose was≥16.7mmol/L, the models were successful. Model rats weredivided into three equal groups randomly(10in each group): modelgroup,XYZ,TLZ. Model rats were fed with HFD which contained with44.4%of sugars,18.6%proteins and22.3%lipids, the rest for minerals and vitamins.HFD were processed into436kcal/100g of granule feedstuff byexperimental animal center of Hebei Medical University. Normal groups werefed with whole value grain feedstuff. After two week of DM models weremade successfully, XYZ and TLZ were given the ZY bygavaging,0.92g/kg,0.77g/kg/d. the rest were given physiological saline bygavaging. Each group was given the medicine for32weeks. At the treatmentof the thirty-two week, We collected24hour urine to measure24hour urinaryprotein quantative,blooding from femoral artery to detection Blood sugar,blood fat and renal function,killing the rats to observe each group ofpathological changes in rat kidneys by light microscopy, Protein expression ofILK and a-SMA in renal tissue was detected using immunohistochemistry.Results:1Weight and hypertrophy index(kidney weight/body weight) of rats in eachgroupCompared with normal group, the model group and treatment group wereunderweight (P<0.05),Model group,XYZ and TLZ had no significantdifferences in rats＇weight (P>0.05); Compared with the normal group, modelgroup hypertrophy index increased significantly (P<0.01), and the modelgroup and two treatment groups no significant differences (P>0.05), tip:model rats, kidney hypertrophy. Tip: model rats, appear kidney hypertrophy.2The24hour urinary protein quantitative of each groupThe24hour urinary protein quantitative of the rats in model group, XYZand TLZ was significantly higher than that of normal group (P<0.01),compared with model group, the24hour urinary protein quantitative of XYZgroup and TLZ was obviously lower (P <0.01), and TLZ was obviously lowerthan that of normal group (P<0.05).3Comparison of the rat＇s FBG,HbAlc,Scr,BUN Compared with normal group, the HbA1c and FBG of the rats in modelgroup, XYZ and TLZ was significantly higher (P <0.01), but there was nodifference among model group, XYZ and TLZ(P>0.05). Compared withnormal group, the Scr and BUN of the rats in model group, XYZ and TLZ wassignificantly higher (P <0.05), compared with model group, XYZ and TLZwas obviously lower (P <0.05), there was no difference between XYZ andTLZ(P>0.05).4Comparison of the rats TC and TGCompared with normal group, the TC and TG of the rats in model group,XYZ and TLZ was significantly higher (P <0.05), compared with model group,the XYZ of TLZ was obviously lower (P <0.01), compared with XYZ, the TCof TLZ was obviously lower (P <0.01),but the TG of TLZ was no difference(P>0.05). Tips: model rats in the presence of abnormal lipid metabolismdisorders, early application of XYZ,and TLZ of herbs can improve lipidmetabolism.5The pathomorphology change of kidneyObservations under light microscope:renal injuries with cellular swelling,flocculi formation,cast formation and inflammatory cells infiltration in renalinterstitium were examined. and tubulointerstitial fibrosis could be seen. TheXYZ and TLZ also showed the similar pathological changes,but thepathological degree was lighter than that in model group.6Expression of ILK in renal tissue by ImmunohistochemicalNormal control rats showed a weak expression of ILK,mainly located inthe distal tubule epithelial cells, glomerular visceral epithelial cells andmesangial cell cytoplasm. Compared with normal group, expression of ILK inmodel group,XYZ and TLZ was significantly higher (P <0.05), compared withmodel group,the XYZ of TLZ was obviously lower (P <0.05), XYZ and TLZno significant differences (P>0.05).7Expression of a-SMA in renal tissue by ImmunohistochemicalThe results detected by immunohistochemistry showed: The expressionof a-SMA in renal vascular smooth muscle in normal group, in renal interstitial, surrounding the atrophic tubules, renal tubular epithelial cells werevisible in the DM rats.model and treatment groups were higher than that innormal group (P<0.01),compared with model group,the expression of a-SMAdecreased (P <0.05), XYZ and TLZ no significant differences (P>0.05).Conclusions:1.TLZ could decrease the DN rat's proteinuria, improve the lipid metabolism.2.XYZ and TLZ can alleviate the pathological changes of DN tubulointerstitiallesion, which could delay the process of DN.3.The expression of ILK and a-SMA was upregulated in renal tubule epithelialcell of DN rats,which is highly related to TEMT. as amediating agent,ILK hasimportant efforts on the positive regulation of process of TEMT.4.XYZ and TLZ can downregulate the expression of ILK and a-SMA in renaltubule epithelial cell of DN rats,which may play its renal protectionmechanism by blocking the TEMT pathway retard renal tubulointerstitialfibrosis. |
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