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Objective The intervention effect of Huoxue Jiedu Huayu Recipe on the pyroptosis of vascular smooth muscle cells(VSMC)on the contralateral renal vessel of 6-month unilateral ureteral obstruction(UUO)rat model was observed,and part of the treatment mechanism of Huoxue Jiedu Huayu Recipe on chronic kidney disease(CKD)was investigated.Methods Forty male wistar rats were randomly divided into 4 groups:the sham operation(Sham)group,the unilateral ureteral obstruction(UUO)group,the eplerenone treatment(EPL)group and the Huoxue Jiedu Huayu Recipe intervention(HJHR)group,10 rats in each group.The EPL group was given eplerenone and the HJHR group was given traditional Chinese medicine.The right kidney was collected after 6 months.Pathological changes were assessed by HE staining and Masson staining.The expressions of Cysteinyl aspartate specific proteinase1(Caspase-1),Interleukin-1β(IL-1β),Serum and glucocorticoid-induced kinase 1(SGK1)and nuclear factor κappa-B(NF-κB)were detected by immunohistochemistry.The DNA damage in renal VSMC was examined by TUNEL staining.Rat VSMCs were used for in vitro experiments.The cells were divided into 4 groups using the random number method:the control(CON)group,the aldosterone(ALD)group,the aldosterone plus eplerenone treatment(EPL)group and the aldosterone plus Huoxue Jiedu Huayu Recipe treatment(HJHR)group.The ALD group was given aldosterone stimulation for 24 h.The EPL group and the HJHR group were given eplerenone and rat serum containing 10%Huoxue Jiedu Huayu Recipe pretreatment before aldosterone stimulation,respectively.The apoptosis rate was detected by flow cytometry.Perforation of gasdermin D(GSDMD)and nuclear translocation of NR3C2(Encode MR)in cell membranes were examined by immunofluorescence.The protein expression of inflammation and pyroptosis-related signaling molecules were examined by western blotting.The mRNA expression of pyroptosis signaling pathway were detected by qRT-PCR.Results Compared with the Sham group,DNA damage of renal blood vessels and VSMCs was increased in UUO group,and expressions of Caspase-1,IL-1β,SGK1 and NF-κB were increased.Compared with the UUO group,the DNA damage of renal blood vessels and VSMCs in EPL and HJHR groups was reduced,and the expressions of Caspase-1,IL-1β,SGK1 and NF-κB were decreased.Compared with the CON group,the ALD group showed pyroptosis and DNA damage of rat VSMC.The expression of NR3C2,NLRP3,Caspase-1,GSDMD,IL-1β,SGK1 and NF-κB was up-regulated.Compared with the ALD group,the pyroptosis and DNA damage were alleviated,and the expression of NR3C2,NLRP3,Caspase-1,GSDMD,IL-1β,SGK1 and NF-κB was decreased in EPL and HJHR groups.Conclusion Huoxue Jiedu Huayu Recipe reduce the vascular damage of the contralateral kidneys of UUO by inhibiting the activation of the MR/NLRP3 inflammasome pathway and inhibiting the pyroptosis of VSMC.
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Aim To observe the effect of eplerenone(EPL) and Chinese decoction on cell apoptosis in obstructive nephropathy rats.Methods Sixty male Wistar rats were randomly divided into sham group, UUO group, EPL group and ZY group(n=15).Except sham group, the rats in the other groups were ligated with unilateral ureteral obstruction(UUO) for renal interstitial fibrosis model.The rats were treated with eplerenone at 100 mg·kg-1·d-1 added to diet in EPL group, and orally 13.7 g·kg-1·d-1 decoction of Chinese medicine in ZY group.The kidneys were harvested on 14th day, the number of renal cell apoptosis were detected by TUNEL, and serum aldosterone and 8-OhdG were detected with radioimmunoassay and ELISA.Caspase-12, caspase-9, Bax and Bcl-2 were examined by immunohistochemistry and Western blot.Results The levels of serum aldosterone, serum and urine 8-OhdG and the number of positive apoptotic cells increased significantly in UUO rats compared with Sham group.The overexpression of caspase-9, caspase-12 and Bax and down-regulated Bcl-2 were obvious in UUO group(P<0.01).The level of 8-OhdG, expression of caspase-9, caspase-12 and Bax were down-regulated, and Bcl-2 expression was up-regulated in eplerenone and Chinese decoction treated rats(P<0.01).Conclusion Eplerenone and Chinese decoction could inhibit cell apoptosis induced by oxidative damage after UUO via caspases and(or) Bax pathway.
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Objective To evaluate the effect of dexmedetomidine on renal functions during the anesthesia of liver transplantation patients.Methods Forty patients (male 31 cases,female 9 cases, aged 40-60 years,ASA grade Ⅱ or Ⅲ)received liver transplantation were randomly divided into two groups(n =20):dexmedetomidine group (group D)and normal saline group (group C).Patients in the group D received a loading dose of dexmedetomidine (0.5 μg/kg within 10 min)and a continuous infusion of dexmedetomidine (0.4 μg·kg-1 ·h-1 )until the end of surgery,while patients in group C received saline.Central venous blood and urine were collected after induction of anesthesia (T1 ),the anhepatic phase of liver 30 min (T2 ),new liver stage 30 min (T3 ),new liver stage 6 h (T4 ),postop-erative 24 h (T5 )and postoperative 1 week (T6 )to detect the serum cystatin C,endogenous creati-nine clearance rate,blood urea nitrogen,blood creatinine,urinary NAG enzyme,urinary albumin, and red blood cells.The use of vasopressors and diuretics,blood loss,fluid,urine,and blood transfu-sion (including RBC,fresh frozen plasma,and platelets)were all recorded.Results Compared with T1 ,serum cystatin C,blood urea nitrogen,serum creatinine of group D increased significantly and en-dogenous creatinine clearance rate reduced significantly at T3 ,T4 (P < 0.05 ).Microalbuminuria in-creased at T3-T5 (P <0.05).Serum cystatin C,blood urea nitrogen,serum creatinine of group C in-creased significantly and endogenous creatinine clearance rate reduced significantly(P < 0.05 ).Com-pared with group C,serum cystatin C,blood urea nitrogen,serum creatinine of group D reduced signif-icantly at T3-T5 and endogenous creatinine clearance rate increased(P <0.05).Microalbuminuria re-duced significantly at T4 ,T5 (P <0.05 ).Perioperative use of diuretics in group D patients was less than that in group C,but the use of vasopressors in group D patients was more than that in group C (P <0.05).Urine volume in group D was more than that in group C (P < 0.05 ).There was no difference in perioperative blood loss, fluid, and blood transfusion between two groups. Conclusion Perioperative continuous infusion of dexmedetomidine might effectively alleviate acute kidney injury during operation and decrease the use of diuretics.
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Aim To observe the effect of mineralocor-ticoid receptor blockade eplerenone on cell proliferation in obstructed kidney of rats. Methods Renal intersti-tial fibrotic animals were made with unilateral ureteral obstruction (UUO) and treated with eplerenone100 mg · kg - 1 · d - 1 . The kidneys were harvested on the 10th day and proliferating cell nuclear antigen ( PC-NA ), serum and glucocorticoid induced kinase-1 (SGK-1 ) and transforming growth factor-β1 ( TGF-β1 ) were detected with immunohistochemistry and Western blot. Results Renal histopathology showed large quantities extracellular matrix (ECM) accumula-tion in kidney with UUO, large numbers of inflammato-ry cells infiltrated in renal interstitium, renal tubular expansion and exfoliation of epithelial cells . The cell proliferation and ECM accumulation were inhibited in eplerenone treated rats significantly. Immunohisto-chemistry and Western blot showed that expressions of PCNA,SGK-1 and TGF-β1 were significantly up-regu-lated with UUO and down-regulated by eplerenone. Conclusion Eplerenone plays the role in inhibiting the cell proliferation and reducing ECM accumulation by down-regulating expression of SGK-1 pathway in rats with unilateral ureteral obstruction.
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Objective To evaluate the blood-saving effect of prophylactic use of tranexamic acid in patients undergoing orthotopic liver transplantation.Methods Sixty ASA physical status Ⅰ-Ⅲ patients of both sexes,aged 18-60 yr,weighing 45-80 kg,scheduled for elective orthotopic liver transplantation,were randomly assigned to one of 2 groups (n =30 each) using a random number table:prophylactic use group (group P) and therapeutic use group (group T).Immediately after induction of anesthesia (T1),at 30 min of anhepatic phase (T2),and at 30 min and 2 h of neohepatic phase (T3,4),central venous blood samples were collected to determine plasma fibrinogen concentration (Fib) and platelet count,and the arterial blood samples were obtained to detect thromboelastography (TEG) parameters.In group T,when lysis after 30 min>7.5% and Clot Index ≤ 1.0 according to the results of TEG,which indicating that primary hyperfibrinolysis occurred,tranexamic acid 15-20 mng/kg was injected intravenously.In group P,immediately after beginning of skin incision,immediately after occlusion of portal vein,and immediately after portal vein unclamping,tranexamic acid 1 g was injected intravenously,and a single injection of tranexamic acid 15-20 mg/kg was given when primary hyperfibrinolysis occurred.The intraoperative blood loss,fluid input and output and transfusion of blood components were recorded.The duration of stay in ICU,amount of abdominal drainage during stay in ICU,volume of blood transfused within 72 h after operation,and hepatic artery and portal vein thrombosis within 1 week after operation were recorded.Results Compared with group T,the intraoperative blood loss,volume of succinylated gelatin injection transfused,and requirement for platelet and cryoprecipitate were significantly reduced,Angle at T2 and lysis after 30 min at T2,3 and maximum amplitude at T3 were increased,and no significant change was found in the duration of stay in ICU,postoperative amount of abdominal drainage and volume of blood transfused in group P.No patients developed primary hyperfibrinolysis in group P.No hepatic artery and portal vein thrombosis was detected within 1 week after operation in the two groups.Conclusion Prophylactic use of tranexamic acid can effectively prevent hyperfibrinolysis and reduce intraoperative blood loss without increasing the risk of development of thrombosis,and it provides better blood-saving effect than therapeutic use guided by TEG in patients undergoing orthotopic liver transplantation.
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Objective:To investigate the protective effects of Compound Danshen Injection and Benazepril on rats with obstructive nephrosis.Methods:The interstitial nephritis model of rat was established by ligating unilateral ureter. The model rats were given drug Compound Danshen Injection and Benazepril, respectively. The levels of angiotensin Ⅱ (Ang Ⅱ), endothelin (ET 1) and the activity of angiotensin converting enzyme (ACE) in renal tissues were measured. Results: The level of angiotensin Ⅱ of Compound Danshen Injection group was 42.03?13.95pg/mg lower that of pathologic group (80.19?27.31pg/mg). The level of Benazepril group was 32.53?8.07pg/mg. There were significant differences among them. The measuring results of ACE and ET 1 were similiar to that of Ang Ⅱ.Conclusion: Compound Danshen Injection and Benazepril can effectively inhibit the activity of ACE and decrease the levels of Ang Ⅱ and ET 1.
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Aim To investigate the role of adrenomedullin on cell proliferation in renal interstitial fibrosis mice. Method Renal interstitial fibrosis model was induced with unilateral ureteral obstruction (UUO) and valsartan(10 mg?kg?d-1) was given by gavage. Immunohistochemistry and RT-PCR were used to detect expressions of PCNA, Col Ⅲ and TGF-?_1 in the kidney of wild type (WT) and adrenomedullin knockout (AMKO) +/-mice. Results The number of PCNA positive cells was increased in WT-UUO group compared with WT sham group and was partially reduced by Valsartan in WT-UUOV group. AMKO group showed higher expression of PCNA than WT group, and it increased more remarkably in AMKO-UUO mice but was reduced by Valsaltan in AMKO-UUOV group. Expressions of Col Ⅲ andTGF-?_1 were upregulated in AMKO-UUO mice, and this change was inhibited by Valsaltan.Conclusion Adrenomedullin play an important role in the process of cell proliferation in renal interstitial pathological changes by UUO.