OBJECTIVES: To investigate the therapeutic mechanism of Danzhi Jiangtang Capsule (DZJTC) for repairing renal vascular endothelial injury in rats with diabetic nephropathy (DN). METHODS: Fifty male SD rat models of DN, established by left nephrectomy, high-sugar and high-fat diet and streptozotocin injection, were randomized into DN model group, low-, medium-, and high-dose DZJTC treatment groups, and DAPT (a γ-secretase inhibitor) treatment group, with 10 rats with normal feeding as the control group. DZJTC was administered by daily gavage at 0.315, 0.63, or 1.26 g/kg, and DAPT (20 mg/kg, dissolved in 50% CMC-Na solution) was given by gavage every other day for 4 weeks; normal saline was given in the control and model groups. After treatment, the levels of creatinine (CRE), blood urea nitrogen (BUN), and microalbuminuria (mALB) were detected with ELISA, and renal pathologies were observed by transmission electron microscopy. Renal expressions of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were measured by immunohistochemistry, and the protein expressions of CD31 and Notch signaling pathway components were detected using Western blotting. RESULTS: The rat models of DN showed significantly increased CRE, BUN, and mALB levels, obvious renal pathologies under electron microscopy, increased renal VEGF, ET-1 and CD31 expressions, and upregulated Notch1, NICD, and MAML1 protein levels. Treatment with DZJTC at the 3 doses and DAPT significantly reduced CRE, BUN, and mALB levels, improved renal pathology, decreased VEGF, ET-1 and CD31 expressions, and lowered Notch1, NICD and MAML1 levels, and the effects were the most pronounced with high-dose DZJTC. CONCLUSIONS DZJTC ameliorates hyperproliferation and dysfunction of renal vascular endothelium in DN rats possibly by regulating renal VEGF and ET-1 levels via inhibiting NICD- and MAML1-mediated Notch signaling pathway.
Animals ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Diabetic Nephropathies/drug therapy* ; Receptor, Notch1/metabolism* ; Kidney/blood supply* ; Diabetes Mellitus, Experimental ; Down-Regulation ; Endothelium, Vascular/metabolism* ; Nuclear Proteins/metabolism*

OBJECTIVE: To observe the effects of a traditional Chinese medicine (TCM) capsule for replenishing qi, nourishing yin and activating blood on Notch/Hes1 signaling pathway in the renal tissue and vascular endothelial CD34 and CD144 expressions in a rat model of diabetic nephropathy. METHODS: Rat models of early-stage diabetic nephropathy were established by left nephrectomy and high- fat and high- sugar feeding combined with intraperitoneal injection of STZ. The rats were randomized into model group, benazepril group, and high-, moderate-, and low-dose TCM capsule groups for corresponding treatments, with 6 normal rats as the control group. After 8 weeks of drug treatment, blood glucose and 24-h urinary albumin of the rats were measured, and the renal histopathology was observed with HE staining; Hes1 expression in the renal tissue was detected with immunohistochemical staining, and the renal expressions of CD34 and CD144 were detected using Western blotting. RESULTS: Compared with the normal control group, the rat models of diabetic nephropathy showed obvious abnormalities in 24- h urinary albumin and expressions of Hes1, CD34 and CD144d. The TCM capsule at both the high and moderate doses significantly reduced 24-h urinary albumin in the rats; the renal expressions of Hes1 and CD34 was significantly reduced in all the dose groups, and the expression of CD144 was significantly reduced in the high- dose group. Compared with benazepril group, the TCM capsule obviously reduced CD34 expression at all the 3 doses and lowered CD144 expression at the low dose. Histopathologically, the rats in the model group showed glomerular hypertrophy, increased mesenteric matrix, thickening and widening of the mesenteric membrane, and nodular hyperplasia. These pathologies were obviously alleviated by treatment with the TCM capsule at the high and moderate doses. CONCLUSIONS The Traditional Chinese medicine (TCM) capsule for replenishing qi, nourishing yin and activating blood can reduce Hes1, CD34 and CD144 in kidney tissue of model rats, play a protective role on kidney function and delay the development of DN.
Animals ; Diabetic Nephropathies ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Qi ; Rats ; Signal Transduction ; Transcription Factor HES-1

OBJECTIVETo improve the treatment for severe open tibia-fibular fracture.

METHODSFrom 1994 to 2000, 146 patients with severe open tibia-fibular fracture were treated. According to Gustilo classification, all patients were of type III. Among them, 96 patients belonged to III A, 36 III B, and 18 III C. One hundred and eight patients were male and 38 female, aged from 11 to 68 years, with an average of 31. All patients were treated with unilateral external fixator combined with simple internal fixation (general screw or Kirschner wire). Thirty patients were treated with secondary flap operation. Among them, 19 patients received pedicle gastrocnemius muscle flaps, 9 free vastus lateralis muscle flaps, and 2 free latissimus dorsi muscle flaps.

RESULTSThree patients of type IIIB were subjected to amputation because of advanced age and associated cerebral or thoraco-abdominal injury. Five patients of type III C had amputation because of insufficient postoperative blood supply and necrosis. The rupture of other 138 patients was well reduced, and firmly fixed. They were followed up for 6 months-6 years, with an average of 2.5 years. The average time of fracture-union was 27 weeks, and the average time for removal of fixtors was 28 weeks. The motion of knee joint ranged from 0 to 120 degree in 110 patients; from 0 to 100 degrees in 25, and from 0 to 90 degrees. The motion of ankle joint was approximately normal.

CONCLUSIONSFor patients with severe open tibia-fibular fracture, comprehensive analysis should be made for preservation of the wounded limb or amputation as for elderly patients with vessel-nerve injury or with cerebral- thoracoabdominal injury, emergency amputation should be done. Unilateral external fixator combined with simple internal fixation (general screw or Kirschner wire) for severe open tibia-fibular fracture is advantageous for a simple and reliable fixation. It is less traumatic.

Adolescent ; Adult ; Aged ; Child ; External Fixators ; Female ; Fibula ; Fracture Fixation, Internal ; Fracture Healing ; Fractures, Open ; surgery ; Humans ; Male ; Middle Aged ; Tibial Fractures ; surgery