Effect of Quyu Chencuo Formula () on Renal Fibrosis in Obstructive Nephropathy Rats / 中国结合医学杂志

OBJECTIVE@#To observe the effect of Quyu Chencuo Formula (, QCF) on renal fibrosis in rats with obstructive nephropathy.@*METHODS@#Twenty-four rats were randomly divided into three groups, 4 for sham operation as the control group, 10 for unilateral ureteral obstruction (UUO) model group, and the rest 10 for QCF treating UUO model group. All rats were sacrificed under 3% pentobarbital (50 mg/kg) anesthesia on the 14th day after surgery, then the right kidney samples of rats were harvested for hematoxylin eosin (HE) staining and Masson staining to observe the renal pathological changes. Immunohistochemistry and Western blotting were used to examine the expression of transforming growth factor β1 (TGF-β1), and real-time polymerase chain reaction (RT-PCR) was employed to examine the expressions of TGF-β1, α-smooth muscle actin (α-SMA) and E-cadherin mRNA.@*RESULTS@#HE and Masson staining showed that the renal interstitial of the rats in the control group had no significant fibrotic lesion; in the model group, there were obvious interstitial fibrosis; for the QCF group, there were epithelial cell necrosis, infiltration of lymphocytes and mononuclear cells, aggravated interstitial fibrosis in varied degrees, but the pathological changes were less in the QCF group than in the model group. The immunohistochemistry and Western blotting results showed that the TGF-β1 expression was increased significantly in the model group, while decreased significantly in the QCF group (P<0.05); RT-PCR showed that the mRNA expression of α-SMA and TGF-β1 increased significantly in the model group, while both were significantly decreased in the QCF group compared with the model group (P<0.05). The mRNA expression of E-cadherin was decreased significantly in the model group, and it was significantly increased in the QCF group as compared with the model group (P<0.05).@*CONCLUSION@#QCF may improve renal fibrosis by regulating the expressions of TGF-β1, α-SMA and E-cadherin, and prevent the progress of kidney fibrosis.

Effect of astragaloside IV based on Toll/MyD88 dependent signaling pathway in treatment of renal fibrosis mice / 中草药

Objective To study the effect of astragaloside IV on renal fibrosis mice with unilateral ureteral obstruction (UUO) and discuss the mechanism. Methods Male C57BL/6 50 mice were divided into five groups randomly, such as Sham-operated group, model group and high-, medium-, and low-dose astragaloside IV groups. From the day of surgery, the mice in astragaloside IV groups (high-, medium- and low-dose) were treated by gavage of astragaloside IV for 2 weeks in doses of 50, 30, and 10 mg/(kg∙d) separately. The mice in Sham-operated group and model group were treated with saline instead of astragaloside IV. Serum creatinine and blood urea nitrogen were detected by chemical methods. Histopathological changes and collagen deposition of affected kidney were observed under optical microscope with HE and MASSON staining. The expression levels of Toll/MyD88 dependent signaling pathway related molecules (TLR4, TLR2, MyD88, TRAF6, NF-Kappa B, TNF-α, and IL-6) in affected kidney were measured by immunohistochemistry and Western blotting methods and observed from protein levels in each group. Results The degree of fibrosis and histopathological damage of affected kidney of mice in model group is the most obvious. And the expression levels of Toll/MyD88 dependent signaling pathway related molecules in affected kidney of mice in model group were the highest. With drug concentration increased in groups of astragaloside IV, in these groups, the injury of affected kidney had been obviously reduced, and the protein expression levels of Toll/MyD88 dependent signaling pathway related molecules (TLR4, TLR2, MyD88, TRAF6, and NF-Kappa B) were also in corresponding reduced, at the same time the expression of terminal inflammatory cytokines (TNF-alpha and IL-6) has been suppressed. Conclusion Astragaloside IV may improve renal interstitial fibrosis in mice after UUO by inhibiting the expression of Toll/MyD88 dependent signaling pathway and release of inflammatory cytokines (TNF-alpha and IL-6).

Ultrastructural Changes of the Uriniferous Tubules after Ureteral Ligation in Rabbits / 대한비뇨기과학회지

This study attempted to clarify the morphological changes of the uriniferous tubules in the postobstructed kidneys of rabbits by electron microscopy. A total of l3 rabbits weighing about 2.5 kg were used. Under penthothal sodium anesthesia, complete ureteral obstruction was accomplished by ligation on the left ureter 1 cm above the ureterovesical junction. The experimental animals were sacrificed at the second and fourth week after the unilateral ureteral ligation. Tissue specimens taken from the renal cortex and medulla were fixed in a mixture of 2% paraform-aldehyde-2.5% glutaraldehyde (phosphate buffer, pH 7.2 ) prior to fixation in 1% osmium tetroxide (phosphate buffer, pH 7.2), and embedded in Epon 8l2. The sections were cut with LKB-III ultratome. Ultra thin sections were contrasted with uranyl acetate and lead citrate, and examine with a JEM-100B electron microscope. The results were as follows: 1. In the 2 weeks group of postobstruction, the abnormal morphology of the uriniferous tubules was: diminution in microvilli and basal invaginations, widening of intercellular space, focal necrosis of the epithelium, desquamation of tubular cells and splitting of the basal lamina. The degenerative changes were severe in the distal tubule, loop of Henle and collecting duct. However, the changes were mild in the proximal tubules. 2. In the 4 weeks group of postobstruction, the degenerative changes were more severe and generalized in all portions of the uriniferous tubules, and focal necrosis and desquamation of the epithelial cells were prominent in the distal tubules and collecting ducts. 3. In both groups of postobstruction, the epithelial cells with mild deformity, such as a decrease of microvilli and basal invaginations, were still preserved in all portions of the uriniferous tubules. From these findings in the obstruct nephropathy, degenerative changes are progressively expedited and partially produced in the urinary tubules.

The Effect of Intravenous E. coli Injection on the Kidney after Ureteral Ligation in the Rat / 대한비뇨기과학회지

This study was designed to observe morphological changes of the renal cortex and medulla of the rat kidneys after intravenous Escherichia coli injection following unilateral ureteral ligation. A total of 105 white rats weighing about 180-200g were used in the experiments. Animals were divided into 3 groups: Escherichia coli injection without ureteral ligation (Group I), unilateral ureteral ligation without intravenous Escherichia coli injection (Group II), and intravenous Escherichia coli injection following unilateral ureteral ligation (Group III). Each group consists of 35 rats. In group I, each rat was injected with about 2 X 10 8 Escherichia coli through the tail vein. In group II, each rat was ligated on the left ureter with silk ligature completely. In group III, each left ureter was ligated and 2 X 10 8 Escherichia coli was injected through the vein of rat tail. Kidneys were obtained 4 hour, 1, 3, 5, 7 days, 2 and 4 weeks after injection of E. coli or ligation of ureter. Specimen of the left kidneys were observed with light microscopy stained with hematoxylin-eosin. 1. In group I, pyelonephritis developed from the 3rd day to the 7th day, after intravenous injection of E. coli, After the 7th day pyelonephritis tended to heal spontaneously. 2. In group II, pyelonephritis developed on the 3rd day after ureteral ligation and inflammatory changes were aggravated progressively thereafter. 3. In group III. renal inflammatory changes were more severe and it progressed faster than in group II. 4. In group II and III, the inflammatory changes were more severe in the renal medulla than in the cortex.

An Experimental Study on Effects of Renal Papillectomy and Partial Ureteral Ligation on the Kidney / 대한비뇨기과학회지

Necrosis of the papilla and chronic interstitial nephritis of the renal cortex are the two renal 1esions most commonly. described in cases of analgesic nephropathy. Some authors believed that the necrosis of the papilla was secondary to the cortical changes by which fibrosis of the cortex produced ischemia of papilla and necrosis. However, other authors have suggested that the pathogenesis is, in fact, the reverse and that the cortical changes in analgesic nephropathy are caused by the medullary necrosis. An experimental study was therefore undertaken to clarify this problem and also to determine the influence of increased intrapelvic pressure on the postpapillectomy renal alterations. Followings are the results: 1. In 'the group having renal papillectomy, marked tubular dilatation and interstitial edema of the medulla are prominent changes upto two weeks after removal of the papilla. Tubules are usu. ally filled with various casts. After three weeks, there starts the tubular atrophy and interstitial fibrosis with mil infiltration of inflammatory cells. The tubular atrophy and renal scarring become much severe and diffuse six weeks after papillectomy. but glomeruli remain relatively intact. 2. The degree of tubular changes and parenchymal scarring are assumed influential to the size of removed papilla. The tubular atrophy is prominent in distal convoluted tubules and collecting tubules, and the interstitial changes extend from the medulla to the cortex in the late stage. 3. Focal or scattered depositions of amorphous calcium or calcium oxalate are found in about one fourth of cases. 4. In the group having partial ureteral ligation a week after renal papillectomy, the tubular and interstitial changes appear earlier and are more remarkable than those of papillectomy alone. The inflammatory reaction is also more prominent, and conglomeration of glomerulus is noted in some instances of the later stage. The form of the renal scarring found in this experimental study closely resembles that seen in analgesic nephropathy in man. This findings support the view that the cortical lesions in analgesic nephropathy develop as a direct consequence of papillary necrosis and additional ureteral ligation enhances interstitial nephritic process. It is possible that the tubular atrophy and interstitial edema that develop shortly after removal of the papilla may produce cortical changes.

Effect of Bilateral Ureteral Ligation and Bilateral Nephrectomy upon Erythropoietin Activity / 대한비뇨기과학회지

It is generally accepted that erythropoiesis is controlled by the erythropoietic stimulating factor (erythropoietin) which is believed being produced in the kidney. Among the various causes. hypoxia is one of the most potent one for the stimulation of erythropoietin production in the kidney. This experiment was planned to determine the efficiency of the erythropoietin in the hydronephrotic kidney and the intact or disturbed liver function. Materials and Methods: The mongrel dogs weighing between 10 and 13 kg were used. Group A: A1: hydronephrosis due to bilateral ureteral ligation. A2: hydronephrosis due to bilateral ureteral ligation and testosterone injection. A3: hydronephrosis due to bilateral ureteral ligation and CCI4 intoxication. Group B: B1' bilateral nephrectomy. B2: bilateral nephrectomy and CCI4 intoxication. To observe the chemical constituents and erythropoietic activity blood sample were collected on 2, 4, 6. 8. 10th day after operation in the A group and 1, 2, 3. 4th day after operation in the B group. Chemical constituents were BUN, creatinine and electrolytes. Erythropoietic activity was determined by the incorporation of 59Fe into the red cells of mouse (DeGowin method). The results of the experiments were summarized as follows: 1. The hydronephrosis due to bilateral ureteral ligation induced increase of erythropoietic activities. 2. When testosterone was given in the group of the hydronephrosis due to bilateral ureteral ligation, erythropoietic activity was increased more than in the group of the hydronephrosis only. 3. The most prominent elevation of erythropoietic activities among any other group was confirmed when liver function was disturbed by CCl4 intoxication in the hydronephrotic animals. This marked elevation seemed to be due to the disturbance of the liver function which inactivated or destroyed erythropoietin. 4. Erythropoietin activity was decreased in the group of bilateral nephrectomy. 5. Erythropoietin activity was much less in the bilateral nephrectcmized group when liver was damaged by CCI. injection. The erythropoietic stimulation was ineffective in the nephrectomized animals. 6. Testosterone injection decreased the BUN and creatinine level in the uremic animals due to nephrectomy. 7. Pathological findings revealed mild hydronephrotic changes in the group of ureteral ligation by. testosterone injection, and mild degree of necrosis and severe fibrosis in the interstitial tissue of the kidney, and fatty changes and focal central necrosis of the liver due to CCl4 injection.

Studies on Restoration of Functional and Morphological Damage of the Kidney Induced by Ureteral Ligation: I. Observation of Angiographic Changes of Experimental Hydronephrosis / 대한비뇨기과학회지

Experimental hydronephrosis in rabbit induced by ureteral ligation a been studied on its development and recovery angiographically. Intrarenal arteries were perfused with 7.5% barium sulfate under pressure from 60mm. to 180mm. Hg over a period of 15-20 minutes after various periods of uretera1 ligation or after release of obstruction and angiographic results were as follows: l. Ligation of ureter for 3 to 7 days maintains almost normal intrarenal vascular architecture though the size of the kidney increases. Deligation restores completely normal vascularity within one Week. 2. Ligation for 1l to 2l days causes irregular pattern of vascular distribution. Restoration begins at one week, significant restoration occurs at two weeks but no complete recovery at three weeks. 3. Ligation for 30 to 60 days looses intrarenal vascular architecture. Restoration seems to begin at two weeks. No complete recovery is observed at three weeks. 4. Size of hydronephrosis and severity of intrarenal vascular changes do not correlate. 5. Intravenous pyelography and radioisotope renography are not very suitable to reveal detailed information on development and recovery process of hydronephrosis.