Progress in Research of Kangxianling Decoction in Delaying Renal Fibrosis / 中国实验方剂学杂志

Renal fibrosis is a common pathological change in the later stages of all kidney diseases. It is a multi-cytokine, multi-signal pathway, multi-factor driven chronic kidney disease. It includes renal interstitial fibrosis, tubular sclerosis and glomerular sclerosis, which eventually leads to chronic renal failure. From health through injury to loss of function, the disease process is closely related to the degree of deterioration of renal function and the prognosis of chronic kidney disease. There is no effective western medicine for the treatment of renal fibrosis. Professor HE Liqun from Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine has summarized the Kangxianling decoction through decades of long-term practical experience. It has the effects in strengthening the spleen and replenishing Qi, clearing away dampness and heat, promoting blood circulation and removing phlegm, and strengthening turbidity. It is composed of Salviae Miltiorrhizae Radix et Rhizoma 15 g, Persicae Semen 12 g, Angelicae Sinensis Radix 12 g, Achyranthis Bidentatae Radix 9 g, Rhei Radix et Rhizoma 15 g. Kangxianling can affect the synthesis and secretion of cytokines and inflammatory factors by expanding blood vessels, and can improve renal tubular fibrosis. It has a good multi-channel, multi-target and multi-directional protective effect on renal function. It also can delay the progress of chronic renal fibrosis by significantly alleviating such symptoms as fatigue and edema in patients with chronic renal fibrosis, and reducing serum creatinine, urea nitrogen and urine protein. In this paper, 5/6 nephrectomy, ischemia reperfusion injury, adriamycin-induced nephropathy, unilateral ureteral obstruction and other different modeling methods are listed. The mechanism of Kangxianling decoction in antagonizing renal fibrosis is discussed and summarized, which further provided new ideas and directions for future clinical and scientific research.

Transplant of bone marrow mesenchymal stem cells via renal artery route in experimental rats with adriamycin-induced nephropathy: comparison of the repair effect on renal function between different times of transplant / 介入放射学杂志

Objective To compare the repair effect on renal function between different times of bone marrow mesenchymal stem cells (BMSCs) transplant via renal artery route in experimental rats with adriamycininduced nephropathy.Methods Adriamycin-induced nephropathy model was established in 32 rats through injection of adriamycin though the caudal vein.Based on the scheduled times of BMSCs transplant,the experimental rats were randomly and equally divided into M0 group (zero time),M1 group (one time),M2group (2 times) and M3 group (3 times) with 8 rats in each group.Other 8 SD rats were used as normal control group (N group).Single dose of 0.5 rnl BMSC suspension (2×106 cells/ml) was transplanted to the rats of M0 group (zero time),M1 group (one time),M2 group (2 times) and M3 group (3 times),for the rats of the groups not receiving BMSC transplant a single dose of 0.5 ml L-DMEM culture medium,used as a placebo,was adopted to replace BMSC suspension.The transplant interval was one week.Before transplant as well as one and two weeks after last time of transplant,the serum urea nitrogen,serum creatinine,24 h urine protein and 24 h urine microprotein were tested,and one week after last time of transplant pathological sections were made for laser focusing microscope examination to observe renal pathological changes and the distribution of BMSC cells in the kidney.Results The values of serum urea nitrogen,serum creatinine,24 h urine protein and 24 h urine microprotein determined at each observation time point in M0 group,M1 group,M2 group and M3 group were significantly higher than those in N group (P＜0.001).The values of 24 h urine protein and 24 h urine microprotein determined at one week after last time of transplant in M2 group and M3 group were strikingly lower than those in M1 group (P＜0.05),but these differences between M2 group and M3 group were not statistically significant (P=0.063).Conclusion For the treatment of adriamycin-induced nephropathy in experimental rats,two times of using BMSCs transplant via renal artery route can achieve optimal curative effect.

Influence of infusion of mesenchymal stem cells by different routes on the expression of AQP1 and AQP2 in rats with adriamycin-induced nephropathy / 介入放射学杂志

Objective To evaluate the therapeutic effect of bone marrow mesenchymal stem cell (MSC) infusion transplantation via renal artery and via caudal vein in treating chronic kidney disease (CKD) in rats,and to compare the expressions of aquaporin1 (AQP1) and aquaporin2 (AQP2) between the two transplantation routes.Methods A total of 50 male SD rats were selected for this experiment.Two experimental rats were used to make preparation of bone marrow MSC.CKD model was established with infusion of adriamycin via caudal vein in 36 rats.The 36 CKD models were randomly divided into adriamycininduced renal failure model control group (A-C group,n=12),MSC transplantation through the right renal artery group (M-A group,n=12) and MSC transplantation through the caudal vein group (M-V group,n=12).The remaining 12 male SD rats were used as the blank control group (N group).One week after the last bone marrow MSC transplantation,the 24 h urine volume,24 h urinary protein content,serum sodium content and serum albumin level were measured,and AQP1 and AQP2 expressions in the kidney tissue were determined by immunohistochemistry.Results Compared with A-C group,the serum albumin level and 24h urine volume in both M-V group and M-A group were significantly increased (P＜0.05),while 24h urinary protein content and serum sodium content were remarkably decreased (P＜0.05).The 24h urinary protein content in the M-A group was obviously lower than that in the M-V group (P＜0.05).The AQP1 and AQP2 expressions in the kidney tissue in both M-V group and M-A group were strikingly lower than those in the A-C group (P＜ 0.05),but no statistically significant differences in AQP1 and AQP2 expressions existed between the M-V group and the M-A group (P＞0.05).Conclusion MSC transplantation can increase serum albumin,and lower urinary protein,serum sodium and the expressions of AQP1 and AQP2 in renal parenchymal cells,which has the effect on repairing renal injury of adriamycin-induced CKD rats.For a given period of time,the clinical curative effect of MSC transplantation via renal artery is better than that of MSC transplantation via peripheral vein,but the difference in curative effect between the two MSC transplantation pathways has no obvious correlation with AQP1 and AQP2 expressions.

Huaiqihuang Granules () reduce proteinuria by enhancing nephrin expression and regulating necrosis factor κB signaling pathway in adriamycin-induced nephropathy / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Huaiqihuang Granules (, HQH), a mixture of Chinese herbs including Trametes robiniophila Murr, Fructus Lycii and Polygonatum sibiricum, on adriamycininduced nephropathy (ADRN) in rats and its underlying mechanisms.</p><p><b>METHODS</b>Rats with ADRN were divided into four groups: the sham group, the model group (distilled water), the low-dose HQH-treated (2 g/kg) group, and the high-dose HQH-treated (4 g/kg) group. Body weight and 24-h urinary protein (Upro) were checked every week. After 5-week intervention, at the end of the study, the rats were sacrificed and blood samples were collected for examination of biochemical parameters, including glomerular morphological makers, podocyte shape, cellular apoptosis, expressions of nephrin, inflammatory and apoptosis markers.</p><p><b>RESULTS</b>HQH ameliorated the rat's general status, proteinuria, renal morphological appearance and glomerulosclerosis. The decreased expression of nephrin in ADRN rats was increased by HQH, as well as the impaired podocyte foot process fusion. Cytosolic levels of p65 and inhibitor of nuclear factor κBα (IκBα) were decreased in ADRN rats, and recovered by the treatment of HQH. Consistently, the induced expression of tumor necrosis factor α (TNF-α), phosphorylated nuclear factor κB p65 (p-NFκB p65) and IκBα in ADRN were markedly suppressed by HQH. In addition, induction of Bax, cleaved caspase-3 and cytochrome C in ADRN rats were suppressed by HQH, indicating the amelioration of apoptosis.</p><p><b>CONCLUSION</b>HQH could ameliorate renal impairments in ADRN rats by increasing nephrin expression, inhibiting NF-κB signaling pathway via the down-regulation of p-NF-κB p65 and p-IκBα, and suppression of glomerular and tubular apoptosis.</p>

Total glucosides of paeony inhibits adriamycin-induced nephropathy in rats through blocking TLR4/NF-κB/TGF-β1 signaling / 中国生化药物杂志

Objective To study effect and its possible mechanism of total glucosides of paeony ( TGP ) on adriamycin-induced nephropathy rats.Methods Thirty male SD rats were randomly divided into normal group ( CON) , adriamycin-induced nephropathy group ( ADRN) and TGP-treated ADRN group (TGP).The rat nephropathy model was established by adriamycin injection.At the end of the 8th week after treatment, ELISA was used to detect the level of Cr and BUN.The values of 24 urine protein was determined by urinary protein kit.Masson staining was used to observe the fibrosis.RT-PCR was used to detect the mRNA levels of TLR4/NF-κB/TGF-β1 .Immunohistochemical method was used to detect the content of TLR4/NF-κB/TGF-β1.ResuIts Compared with the CON group, the level of Cr, BUN, 24 urine protein of ADRN group rised(P<0.01), the degree of fibrosis of ADRN group were aggravated(P<0.01), and the expressions of TLR4/NF-κB/TGF-β1 of ADRN group increased significantly.However, compared with ADRN group, the(P<0.01) level of Cr, BUN, 24 urine protein of TGP-treated rats reduced(P<0.01), the degree of fibrosis of TGP-treated rats eased(P<0.05), and the expressions of TLR4/NF-κB/TGF-β1 of TGP-treated rats decreased significantly.ConcIusion TGP retards the process of fibrosis and reduces the pathological damage in adriamycin-induced rats by down-regulating the expression of TLR4/NF-κB/TGF-β1 signaling.

The Influence of Different Infusion Methods of Bone Marrow Mesenchymal Stem Cells in Adriamycin Nephropathy Rat Model / 天津医药

Objective To investigate the effectiveness of bone marrow mesenchymal stem cell (MSC) and different transplantation methods of MSC on adriamycin (ADR) model of nephropathy in rats. Methods The ADR model of nephrop-athy was induced by left nephrectomy plus injection of ADR (2.5 mg/kg) in Sprague-Dawley (SD) rats, once a week for two weeks. The model rats with nephropathy were randomly divided into three groups: adriamycin nephropathic model control group (ADR, n=12), MSCs transplantation through right renal artery group (M-A, n=12) and MSCs transplantation through peripheral veins group (M-V, n=12). Another 12 SD rats were served as normal controls (N, n=12). MSCs were cultured, transplanted via right renal artery (2×106/mL) to rats in M-A group, and were transplanted via peripheral veins 2×106/mL) to rats in M-V group. The same procedure was repeated in two weeks. The blood urea nitrogen, serum creatinine, 24 h urine protein and 24 h uromicroprotein were detected before transplantation and in one and two weeks after the second transplanta-tion. The renal morphology and labeled cells were examined in the kidney one week after the second transplantation. Results The values of blood urea nitrogen, serum creatinine, 24 h urine protein and 24 h uromicroprotein were significant-ly higher in M-A group, M-V group and ADR group than those of N group (P<0.01). The level of 24 h uromicroprotein was significantly lower before the second transplantation in M-A group than that of ADR group (P<0.01). The serum level of cre-atinine was significantly decreased in M-A group than that of ADR group and M-V group (P<0.01). The levels of 24 h urine protein and 24 h uromicroprotein were significantly lower after one week transplantation in M-A group than those of M-V group (P<0.01). The serum level of creatinine was significantly lower two weeks after the second transplantation in M-A group than that of ADR group and M-V group (P<0.01), but no significant differences in the levels of urine protein and uro-microprotein between M-A group and M-V group. Conclusion Transplantation of MSCs can alleviate renal damage of chronic ADR-induced nephropathy, which is more effective in rats with MSCs transplantation via renal artery than that in rats with MSCs transplantation via peripheral vein.

Efficacy research of immune inhibitors sequential therapy according to the cell cycle for the adriamYcin-induced nephropathy rats / 中华肾脏病杂志

Objective To assess the efficacy of different sequential therapy regimens according to the theory of cell cycle on adriamycin-induced nephropathy (AIN) rats. Methods SD rats were randomly divided into five groups:control group (n=8),AIN model group (n=8),MP+ CsA+MMF group (n=8),MP+CsA+CTX treated group (n=8) and MP+FK506+Rapa group (n=8).The levels of 24-hour urinary protein,serum total protein (TP),albumin (Alb),cholesterin (Chol),triglyeride (TG),serum urea nitrogen (BUN),serum creatinine (Scr) were measured.The renal pathological changes were observed by light microscope.The expressions of nephrin and podocin were analyzed by immunohistochemistry and real-time PCR.The expression of CTGF was detected by Western blotting. Results (1)Compared with control group,the levels of 24-hour urinary protein in AIN model group were obviously increased at 2nd,4th,8th and 12th week (all P＜0.01).The level of 24-hour urinary protein were obviously decreased in treatment groups at 8th and 12th week than those in AIN model group (all P＜0.05). (2)The levels of TP and Alb were significantly lower in AIN model group than those in control group (all P＜0.01),and the levels of TG and Chol were significantly higher in AIN model group than that in control group (all P＜0.01).The levels of TP and Alb were significantly higher and the levels of TG and Chol were significantly lower in treatment groups than those in AIN model group (all P ＜0.05). (3)The results of immunohistochemistry indicated the expressions of nephrin and podocin in treatment group rats were obviously higher than those in AIN model group (all P＜0.01). (4)The results of Western blotting indicated the expression of CTGF in treatment group rats was higher than that in AIN model group (P＜0.05).The effect of inhibitting fibrous degeneration in MP +FK506 +Rapa group was more greater than other treatment groups. Conclusions Sequential combined regimens according to the cell cycle can improve the pathological change in adriamycin-induced nephropathy rats,reduce the urine protein,increase the levels of TP and Alb,decrease the levels of TG and Chol,increase the expression of nephrin and podocin,and ameliorate kidney fibrosis.

Rhodiola decreases the expression of ?-smooth muscle actin in tuhulointerstitial of adriamycin-induced nephropathy rats / 基础医学与临床

Objective To find the effect of Rhodiola herb on the phenotypic transfer of epithelial cell in renal tubule of adriamycin-induced nephropathy rats.Methods The rat nephropathy model is established by adriamycin.For Rhodiola herb treated group,feed with Rhodiola herb 0.672 g/kg?d from the 4th week,for the control group and neohropathy group,feed with water [3 mL/(kg?d)].Kill the rats per batch at the week of 4th,8th,12th,16thand 20th week,observe the pathological change of nephridial tissue,test the expression of ?-SMA-protein of myofibroblast in the tuhulointerstitial.Results A semi-quantitative analysis of ?-SMA of rats at the 16th week in the nephropathy group is 6.24?0.57,which is obviously higher than that of Rhodiola herb treated group,3.84?0.28(P