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OBJECTIVE：To st udy preventive effect and mec hanism of ginsenoside Rg 1 on focal cerebral ischemia-reperfusion injury（CIRI）model rats. METHODS ：Totally 78 SD rats were randomly divided into sham operation group ，model group ， butylphthalide control group （positive control ，10 mL/kg），ginsenoside Rg 1 low-dose，medium-dose and high-dose groups （10， 20，40 mg/kg），with 13 rats in each group. Administration groups were give relevant medicine intraperitoneally ，sham operation group and model group were given constant volume of normal saline intraperitoneally ，once a day ，for consecutive 7 d. After medication，except for the sham operation group ，focal CIRI model was induced by middle cerebral artery occlusion （MCAO） method in other groups. After modeling ，neurological deficit scoring was performed according to the modified neurological difict scoring standard ； TTC staining was used to detected the percentage of cerebral infarction of rats ；the cerebral water content was measured by dry/wet weight method ；serum contents of IL- 1β and IL-6 were detected by ELISA ；the protein expressions of p-p 38 MAPK and p-NF-κB p65 in cerebral tissue were determined by immunohistochemistry and Western blotting assay. RESULTS ： Compared with sham operation ，neurological deficits score ，percentage of cerebral infarction and cerebral water content ，serum contents of IL- 1β and IL-6，positive expression numbers of cells and protein expressions of p-p 38 MAPK and p-NF-κB p65 in cerebral tissue were increased significantly in model group （P＜0.05 or P＜0.01）. Compared with model group ，above index levels of administration groups were all decreased significantly （P＜0.05 or P＜0.01），and the effect of ginsenoside Rg 1 had a dose-dependent trend ；there was no significant difference of all above indexes between ginsenoside Rg 1 middle-dose，high-dose groups and butylphthalide control group （P＞0.05）. CONCLUSIONS ：Ginsenoside Rg 1 has a certain preventive effect on focal CIRI model rats ，the mechanism of which may be associated with down-regulating the protein expression of p-p 38 MAPK and p-NF-κB p65，inhibiting the release of inflammatory factors such as IL- 1β and IL-6.
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The aim of this paper was to investigate the immunosuppressive effects of dihydroartemisinin and Huobahua compatibility in mice with delayed hypersensitivity and explore its possible mechanism. The delayed-type hypersensitivity(DTH) model in mice was established to observe the immunosuppressive effects of dihydroartemisinin and Huobahua compatibility in DTH mice. ELISA assay was used to detect the contents of interferon(IFN-γ); histopathological changes and degree of mononuclear infiltration of right ear tissues were examined by HE staining; the expression level of intercellular cell adhesion molecule-1(ICAM-1) in the right ear of mice was detected by immunohistochemistry; the protein expression levels of p38 phospho mitogen activated protein kinase(p-p38 MAPK) was detected by Western blot analysis. As compared with the control group, the degree of ear swelling, thymus/spleen index, serum IFN-γ as well as the number and degree of infiltration of monocytes were significantly increased in the model group. As compared with the model group, the degree of ear swelling and thymus/spleen index of the mice in the combination group were significantly reduced; the number and degree of infiltration of monocytes were significantly relieved; the serum levels of IFN-γ and the expression levels of p-p38 MAPK and ICAM-1 proteins in the right ear were also significantly reduced. The combination of dihydroartemisinin and Huobahua can significantly inhibit the DTH response, and it may regulate the production and secretion of related inflammatory factor IFN-γ by inhibiting the phosphorylation activity of p38 MAPK, thereby further reducing the expression of ICAM-1 and thus exerting the immunosuppressive effect.
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Animals , Mice , Artemisinins , Intercellular Adhesion Molecule-1/genetics , Monocytes , p38 Mitogen-Activated Protein Kinases/geneticsABSTRACT
Objective: To explore the protective effect and mechanism of modified Dahuang Zhechong Wan on renal interstitial fibrosis in rats with obstructive nephropathy. Method: The unilateral ureteral ligation (UUO)-induced renal interstitial fibrosis model was adopted, 50 SD rats were randomly divided into 5 groups:sham operation group, model group, enalapril group (0.001 g·kg-1), and high and low-dose modified Dahuang Zhechong Wan group (19, 9.5 g·kg-1). Rats in each group were put to death on the 15th day after operation. The serum levels of serum creatinine (SCr) and urea nitrogen (BUN) were collected by enzyme method. The 24-hour urine was collected for 24-hour urinary protein quantity(24 h-Upro) by pyrogallol red molybdenum end point. The kidney tissue was removed from the ligated side. Hematoxylin-eosin (HE) staining and Masson staining were performed; the expressions of transforming growth factor-β1 (TGF-β1), fibronectin (FN) and α-smooth actin (α-SMA) were determined by immunohistochemistry (IHC). Expressions of TGF-β1, p38 mitogen-activated protein kinase (p38 MAPK) and phosphorylated p38 MAPK (p-p38 MAPK) were detected by Western blot. Result: Compared with Sham group, UUO group showed a significant increase in 24 h-Upro, SCr, and BUN (Pβ1, FN, and α-SMA were increased obviously (Pβ1, p38 MAPK, and p-p38 MAPK were increased obviously (PPβ1, FN and α-SMA decreased obviously (Pβ1 and p-p38 decreased obviously (PConclusion: Modified Dahuang Zhechong Wan may improve renal interstitial fibrosis by reducing the high expressions of FN and α-SMA, down-regulating the expressions of p-p38 MAPK and TGF-β1 in p38 MAPK signaling pathway, and decreasing extracellular matrix over deposition and renal cell damage.
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Objective To study the effects of Xianlu Qige Decoction combined with acupuncture on the improvement of cervical intervertebral disc symptoms (CIDS) and serum phosphorylation-P38 mitogen-activated protein kinase (p-P38MAPK). Methods A total of 156 patients with CIDS admitted to our hospital from April 2016 to September 2018 were enrolled. The patients were randomly divided into two groups, 78 cases for each. The control group was given conventional Western medicine treatment. The observation group was given the combination of Xianlu Qige Decoction and acupuncture. The acupuncture therapy was supervised, by comparing the total effective rate of the two groups before and after treatment. The Tianzhong Jingjiu cervical spondylosis symptom scale 20 points score, serum immunoinflammatory factors [immunoglobulin G (IgG), IgA, IgM, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1, p-P38 MAPK pathway protein expression [vascular endothelial growth factor (VEGF), matrix metalloproteinase-3 p-P38MAPK, MMP-9], serum pain medium [nitrogen monoxide (NO), serotonin (5-HT), and prostaglandin E2 (PEG2)] levels were compared. Results The total effective rate of the experimental group was 94.87% higher than that of the control group of 76.92% (P < 0.001). After treatment the scores of symptoms, signs, work and life ability and hand function of the two groups were higher than those before treatment, and the scores of pain were lower than those before treatment (P < 0.05). After treatment, the scores of symptoms, signs, work and life ability and hand function in the experimental group were higher than those in the control group, and the scores of pain were lower than those in the control group (P < 0.001); the levels of IgG, IgA, IgM, TNF-α, IL-1 and IL-6 in the two groups were lower than those before treatment (P < 0.001); the levels of IgG, IgA, IgM, TNF-α, IL-1 and IL-6 in the experimental group were lower than those in the control group (P < 0.001). After treatment, the levels of vascular endothelial growth factor (VEGF) in both groups were lower than those before treatment, and the levels of MMP-3, p-P38MAPK and MMP-9 were higher than those before treatment (P < 0.001); after treatment, the levels of VEGF in the experimental group were lower than those in the control group, and the levels of MMP-3, p-P38MAPK and MMP-9 were higher than those in the control group (P < 0.001). After treatment, the levels of NO, PEG2 and 5-HT in the two groups were lower than those before treatment (P < 0.05); After treatment, the levels of NO, PEG2 and 5-HT in the experimental group were lower than those in the control group (P < 0.05). Conclusion Xianlu Qige Decoction combined with acupuncture in the treatment of CIDS can reduce the release of serum pain media, significantly improve the clinical symptoms such as pain, and inhibit the inflammatory response of body, and its curative effect is significant. The mechanism may be related to the regulation of p-P38MAPK signaling pathway.
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Objective To discuss the effect of breast cancer anti-estrogen resistance 1(BCAR1) knockdown on the expression of P38 and p-P38 in lung cancer cell line A549. Methods A549 cells (control group), A549 cells with RNAi letiviral vector of BCAR1 (interference group) and A549 cells with negative control letiviral vector (negative group) were cultured. Western blot was used to detect the expression of P38 and p-P38. The prolifera-tion,cell cycle,migration and invasion were measured by colony formation assay,flow cytometer,transwell experi-ment and scratch adhesion test,respectively. Results p-P38 expression in interference group cells was significant-ly lower than that in other two group cells(P<0.05).G1phase of interference group cells was significantly increas-ing than that in other two group cells(P<0.05).The proliferation,migration and invasion of interference group cells were all significantly suppressed as compared with that of other two group cells(P<0.05). Conclusions BCAR1 knockdown decreases p-P38 expression and inhibits proliferation,migration and invasion of A549 cells.
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Aim To investigate the effect of baicalein on the reversal of multidrug resistance ( MDR) media-ted by breast cancer resistance protein ( BCRP) in hu-man breast cancer MCF-7/MX cells, and explore the possible mechanisms. Methods MTT assay was per-formed to determine the cytotoxicity of baicalein and susceptibility of chemotherapeutic drugs. The protein expression levels of BCRP, p-p38 MAPK and NF-κB p65 were determined by Western blot. Results MCF-7/MX cells were not only resistant to MX but cross-re-sistant to 5-FU and DDP, and the resistance index was 70. 45, 6. 68 and 21. 47, respectively. 2. 5, 5μmol· L-1 of baicalein could increase the sensitivity to above chemotherapeutic agents and decrease the expression levels of BCRP, p-p38 MAPK and NF-κB p65 in MCF-7/MX cells. Conclusion Baicalein can effec-tively reverse MDR of MCF-7/MX by down-regulating BCRP expression through p38/MAPK and NF-κB path-ways.
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Objective To study the effect of curcumin on the expression of inflammatory factors in model rats with chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS) type Ⅲ.Methods The rats were randomly divided into following groups: sham-operated group(sham), CP/CPPS model group(model), curcumin 50 mg group(cur-50 mg) and curcumin 100 mg group(cur-100 mg) and p38 inhibitor group(SB203580).Drug was given to each treatment group for 12 days by intraperitoneal injection.The levels of TNF-α, p38, COX-2 mRNA was measured by Real-Time PCR.The expressions of TNF-α and COX-2 proteins were measured by immunohistochemistry.The levels of p38, p-p38 and NF-κB proteins were detected by Western blot.Results NF-κB, p-p38, TNF-α, COX-2 proteins and TNF-α, p38, COX-2 mRNA in model group were higher than those in the sham group (P<0.01);cur-100 mg group and SB203580 group could significantly relieve these change in the model group (P<0.01);COX-2 mRNA and protein in cur-100 mg group decreased more than that in SB203580 group;p-p38 was positively correlated with NF-κB in curcumin groups and SB203580 group compared with model group (P<0.01).Conclusions Curcumin can reduce the expression of inflammatory cytokines NF-κB, TNF-α, COX-2 and p-p38 in rats with CP/CPPS type Ⅲ.
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Objective To explore the relationship between the protective effect of hydrogen sulfide (H2 S ) postconditioning against myocardial hypoxia-reoxygenation and the dynamics of actin. Methods Adult rat cardiomyocytes were isolated and the same hatch cells were divided into 4 groups (n =3):normal group (group N),hypoxia-reoxygenation group (group HR),ischemia postconditioning group (group IPTC)and H2 S postconditioning group (group S).The four groups were divided into two sub-groups with or without cytochalasin D (CyD).At the end of reoxygenation,F-actin/G-actin,intracellular calcium ion concentration (Ca2+ )and pH value were detected with laser scanning confocal microscopy, meanwhile the level of p-p38MAPK was detected with Western blot.Results The fluorescence intensity of F-actin/G-actin of group HR,group IPTC and group S were significantly higher than that of group N (P <0.05).The fluorescence intensity of Ca2+ of group HR was higher than that of group N,group IPTC and group S (P <0.05);The intensity of Ca2+ of all group with CyD treatment was higher than those without (P <0.05);The fluorescence intensity of pHi of group N and group HR with CyD treatment was higher than those without;The fluorescence intensity of pHi of group IPTC and group S was lower than those without;The flu-orescence intensity of pHi of group HR was lower than that of group N,group IPTC and group S (P <0.05), respectively;the pHi of group N and group HR sub-group with CyD treatment was higher than those without correspondingly (P <0.05),however,the pHi of IPTC and S sub-groups were lower than their corresponding groups (P <0.05).The level of p-p38MAPK in group HR was significantly higher than those of other groups (P <0.05);there was no difference among groups N,IPTC and S.Conclusion Hydrogen sulfide postcondi-tioning could promote F-actin to remodel and stabilize the cellular environment.Hypoxia-reoxygenation pro-motes the phosphorylation level of p38MAPK,which could be surpressed by H2 S postconditioning.
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OBJECTIVE@#To explore the causes of immune dysfunction in neonatal rats with hyperbilirubinemia.@*METHODS@#A total of 60 newborn SD rats were equally randomized into normal saline (NS) group, LPS control group, bilirubin control group, low-dose group and high-dose group. After anesthesia, 0.1 mL NS was given to the NS and LPS control group and different doses of bilirubin for the other groups; 1 h later, the NS and bilirubin control group received the intraperitoneal injection of 0.05 mL NS and 1mg/kg LPS for the other groups. After 5 or 24 hours of model establishment, spleens were collected for detecting the expression levels of MyD88 and p-TAK1 protein and the spleen cells apoptosis by immunohistochemmistry and TUNEL method. After 24 hours of model establishment, serum inflammatory factors levels and T cell subsets distribution were determined by ELISA and flow cytometry.@*RESULTS@#In contrast to low-dose bilirubin, high-dose bilirubin could induce spleen cells apoptosis in coordination with LPS. After 5 hours of model establishment, compared with NS group, MyD88 expression level in low-dose group elevated while p-TAK1 level in high-dose group reduced (P<0.05). In high-dose group, inflammotory factors levels and CD8(+) T cells percentage were all higher than LPS control and NS group (P<0.05), while CD4(+) T cells percentage was lower than NS group (P<0.05).@*CONCLUSIONS@#High-concentration plasma bilirubin in coordination with LPS could inhibit NF-κB signal pathways activation and aggravate inflammatory reaction, thus caused immunosuppression with inflammation cascade, which resulted in the immune dysfunction.
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Objective:To explore the causes of immune dysfunction in neonatal rats with hyperbilirubinemia.Methods: A total of 60 newborn SD rats were equally randomized into normal saline (NS) group, LPS control group, bilirubin control group, low-dose group and high-dose group. After anesthesia, 0.1 mL NS was given to the NS and LPS control group and different doses of bilirubin for the other groups; 1 h later, the NS and bilirubin control group received the intraperitoneal injection of 0.05 mL NS and 1mg/kg LPS for the other groups. After 5 or 24 hours of model establishment, spleens were collected for detecting the expression levels of MyD88 and p-TAK1 protein and the spleen cells apoptosis by immunohistochemmistry and TUNEL method. After 24 hours of model establishment, serum inflammatory factors levels and T cell subsets distribution were determined by ELISA and flow cytometry.Results: In contrast to low-dose bilirubin, high-dose bilirubin could induce spleen cells apoptosis in coordination with LPS. After 5 hours of model establishment, compared with NS group, MyD88 expression level in low-dose group elevated while p-TAK1 level in high-dose group reduced (P<0.05). In high-dose group, inflammotory factors levels and CD8+ T cells percentage were all higher than LPS control and NS group (P<0.05), while CD4+ T cells percentage was lower than NS group (P<0.05).Conclusions:High-concentration plasma bilirubin in coordination with LPS could inhibit NF-κB signal pathways activation and aggravate inflammatory reaction, thus caused immunosuppression with inflammation cascade, which resulted in the immune dysfunction.
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Objective: To explore the causes of immune dysfunction in neonatal rats with hyperbilirubinemia. Methods: A total of 60 newborn SD rats were equally randomized into normal saline (NS) group, LPS control group, bilirubin control group, low-dose group and high-dose group. After anesthesia, 0.1 mL NS was given to the NS and LPS control group and different doses of bilirubin for the other groups; 1 h later, the NS and bilirubin control group received the intraperitoneal injection of 0.05 mL NS and 1mg/kg LPS for the other groups. After 5 or 24 hours of model establishment, spleens were collected for detecting the expression levels of MyD88 and p-TAK1 protein and the spleen cells apoptosis by immunohistochemmistry and TUNEL method. After 24 hours of model establishment, serum inflammatory factors levels and T cell subsets distribution were determined by ELISA and flow cytometry. Results: In contrast to low-dose bilirubin, high-dose bilirubin could induce spleen cells apoptosis in coordination with LPS. After 5 hours of model establishment, compared with NS group, MyD88 expression level in low-dose group elevated while p-TAK1 level in high-dose group reduced (P+ T cells percentage were all higher than LPS control and NS group (P+ T cells percentage was lower than NS group (P<0.05). Conclusions: High-concentration plasma bilirubin in coordination with LPS could inhibit NF-κB signal pathways activation and aggravate inflammatory reaction, thus caused immunosuppression with inflammation cascade, which resulted in the immune dysfunction.
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Aim To explore the effect of knockdown spinal cord LCN2 by RNAi on the development of mor-phine tolerance in normal rats.Methods After suc-cessful intrathecal implantation, fourty-eight male Sprague-Dawley rats weighing 1 80 -220 grams were randomly divided into 4 groups (n =1 2):group I:control group,group II:morphine tolerance group, group Ⅲ:mismatch siRNA group,group IV:LCN2 siRNA group.The sixth day after intrathecal implanta-tion,rats were tested to ensure the position of cathe-ters,and it was recorded as d 0.On d 2 -8,rats were subcutaneously (s.c)injected of normal saline (NS) (group I)or morphine (group Ⅱ,Ⅲ,Ⅳ)1 0 μg· g -1 twice a day at 8:00 and 1 6:00.Before everyday s. c injection,rats were intrathecally injected of 1 0 μL DEPC solution (group Ⅰ,Ⅱ),1 0 μL DEPC solution containing 4 μg mismatch siRNA (group III)and 4 μg LCN2 siRNA solution (group IV).Paw withdrawal la-tencies to thermal stimuli (PWTL)were tested before morphine injection and 45 minutes after morphine in-jection on d 1 and d 9.The percentage of maximal pos-sible effect (% MPE)was calculated later.Animals were sacrificed on d 9 after the behavioral test and the lumbar enlargement segments of the spinal cord were removed for detecting the expression of phosphorylated-p38 mitogen-activated protein kinase (p-p38 MAPK) and LCN2 by Western blot and microglia marker Iba1 by immunofluorecence.Results On d 1 ,there was no significant difference in %MPE among four groups. On d 9,compared to group Ⅰ,%MPE was signifi-cantly reduced (P <0.05)while p-p38MAPK,LCN2 and Iba1 were markedly up-regulated in group Ⅱ andⅢ (P <0.05 ).On d 9,compared to group Ⅱ,%MPE was significantly increased while p-p38MAPK, LCN2 and Iba1 were markedly reduced in group IV (P<0.05).Conclusion Using LCN2 siRNA to knock-down spinal LCN2 relieves the development of mor-phine tolerance in normal rats possibly through inhibi-ting the activation of microglia and p38 MAPK in the spinal cord.
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Objective To observe the effect of astragaloside IV (A) and SB203580 antagonize cadmium (Cd) toxicity on expression of associated protein and blood-testis barrier(BTB) in rats and to study the protective mechanism of A on it.Methods Totally 21 SD male rats were randomly divided into 7 groups, 3 rats per group:Cd [ intraperitoneally injected with 0.1%CdCl2,1mg/(kg?d)],Cd+A [at the above dose of CdCl2,at the same time with A,10mg/(kg?d)], and Cd +SB203580 [at the above dose of CdCl2,at the same time with SB203580,100μg/(kg?d)], each of the above groups was further divided into continuous five and ten days treatment groups .The control group was intraperitoneally injected with equal dosage of normal saline .The testes were studied by light , electron microscopy , immunohistochemistry and Western blotting .Results In the control group ,irregular and lightly stained nuclei of Sertoli cell ( Sc) in seminiferous tubules were observed by HE staining .A continuous electron density line of tight junction ( TJ) and normal ultrastructure of BTB were observed .After Cd treatment ,the vesicular formation in the Sc was observed .The ultrastructural damage of Sc and TJ was observed .Compared with the corresponding time point of Cd group ,these were weakened in morphology of testis and ultrastructure of TJ after Cd +A or Cd +SB203580 treatment .The positive products of zonula occludens-1 ( ZO-1 ) and claudin-11 were localized mainly in the base of the seminiferous tubule .After Cd treatment , the average absorbance (AA) of ZO-1 and Claudin-11 was decreased significantly compared with that of the control group (P<0.05).After Cd +A or Cd +SB203580 treatment,AA of ZO-1 and Claudin-11 were increased significantly compared with that of the Cd group(P<0.05),though lower than that of the control group .The result of Western blotting showed that phosphorylation-p38MAPK in Cd group was increased significantly compared with that of the control group (P<0.05).After Cd +A or Cd+SB203580 treatment, it was decreased significantly compared with that of the Cd group (P<0.05).Conclusion Cd decreases ZO-1 and Claudin-11 expression and damages ultrastructure of TJ in BTB , asⅣhas protective effect on it , and is related to inhibiting activation of p 38 MAPK pathway .
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Objective To investegate the effect of phosphorylated-P38 MAPK(mitogen-activated protein kinase) on the expression of caspase-3 in the substania nigra (SN) of MPTP-induced mouse model of(PD). Methods Mice were randomly divided into MPTP model group, which were treated with MPTP and inhibitor group. Once a day for 5 days; control group was treated with saline and DMSO as much as the model group received per day for 5 days. The behavioral were observed, immunohistochemistry and Western blot for TH, caspase-3 and phosphorylation of P38 MAPK were used to observe the change of positive cell number and the expression level in the SN of midbrain. Results Compared with the mice in control group, the model group showed typical symtoms of PD with decreased numbers of TH-positive neurons and the protein level of TH in SN of the midbrain by about 60% and 65% respec-tively(P<0.01) , the numbers of caspase-3 and phosphorylation of P38 MAPK immunoreactive cells and their protein level in the SN of the midbrain increased markedly (P<0.01). After giving SB203580, the above changes were reduced obviously (P <0. 01). Conclusion In the mouse model of subacute Parkinson's disease induced by MPTP, phosphorylated-P38 MAPK regulated caspase-3 in the SN of midbrain, the specific P38 MAPK inhibitor SB203580 is neurologically oprotective to the mouse model.
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Objective To study the expression and the significance of phosphorylated P38(p-P38) and uPA in breast cancer tissues.Methods Immunohistochemistry(S-P) was used to test the protein expression of p-P38 and uPA in 60 specimens from 50 patients with breast cancer.Western blotting was adopted to detect the protein expression of p-P38 and uPA in breast cancer cells and uPA protein expression after incubation with SB203580,an specific inhibitor of P38 MAPK blocked P38 MAPK signaling pathway.Results The positive rates of p-P38 protein and uPA protein in breast cancer tissues were 56.7%and 60.0% respectively.The protein expression level of p-P38 and uPA in breast cancer tissues was significantly higher than that in adjacent normal tissues(P
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Aim To investigate the effect and mechanism of valdecoxib on the apoptosis of human esophageal cancer cells.Methods Flow cytometry was used to observe the effect of valdecoxib on apoptosis and the cell cycle distribution of Eca109 cells.Transmission electron microscope was further used to detect the cell apoptosis.The content of LDH was examined using LDH kit.The expressions of p-p38MAPK,Fas and FasL protein were detected using flow cytometry.Results Valdecoxib of 25～400 ?mol?L~(-1) significantly induced the apoptosis of Eca109 cell line,and the rate of apoptosis was increased from(2.95?0.83)% to(48.46?0.73)%,50～400 ?mol?L~(-1) valdecoxib also decreased the proliferation index and the proportion of cells in the S phase,increased the proportion of cells in the G_0/G_1 phase,but had no effect on the proportion of cells in the G_2/M phase.Compared with those in Eca109 cells cultured in the medium with solvent,the expression of p-p38MAPK,Fas and FasL was higher in the Eca109 cells exposed to valdecoxib in a dose-dependent manner in 72 h.Conclusion Valdecoxib can induce apoptosis of Eca109 cell line partly by up-regulating the expression of p-p38MAPK/Fas/FasL.
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Aim To investigate the effect of irbesartan and spironolactone on expressions of connective tissue growth factor(CTGF),P-p38MAPK proteins during vascular remodeling in renovascular hypertensive rats(RHR).Methods Renovascular hypertension was induced by two kidney one clip(2K1C)operation.8 weeks later,RHRs were given irbesartan or(and)spironolactone for 8 weeks.After 8 weekstreatment,the morphometric measurements were performed in the mesenteric arterioles.Concertration of carboxyterminal propeptide of typeⅠprocollagen(PⅠCP)and N-terminal propeptide of type Ⅲ procollagen(PⅢNP)in blood serum was measured by enzyme linked immunosorbent assay method,and the media collagen area was assessed by collagne-specific Picro-sirius red staining with computerized video processing.Expressions of collagen type I,CTGF,P-p38MAPK proteins were detected using immunohistochemistry respectively.Results The arterial systolic pressure was attenuated significantly after the treatment of irbesartan,and this effect could not be enhanced by spironolactone.The media thickness over lumen ratio,media cross-sectional area over luminal area ratio of mesenteric arterioles,concertration of PⅠCP and PⅢNP,media collagen area,and expression of collagen typeⅠwere significantly increased in RHRs but ameliorated by irbesartan and spironolactone.Meanwhile,the expressions of CTGF,P-p38MAPK proteins were up-regulated in RHRs but blunted significantly after the treatment of irbesartan and spironolactone.The combined treatment had the synergic effects.Conclusions There is a synergistic effect of attenuating extracellular matrix(ECM)producing and amelioration of vascular remodeling(VR)by combined use of irbesartan and spironolactone.It maybe related to the expressions of CTGF and P-p38MAPK proteins down regulated by these two drugs.
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Objective To investigate the effect and underling mechanism of genistein(GEN)on adipogenesis in 3T3-L1 preadipocytes.Method 3T3-L1 preadipocytes were induced to differentiate in the presence of vehicle(MDI),GEN or SB203580.On D 6 after induction of differentiation,lipid accumulation was assessed using the dye Oil Red O,medium was collected and assayed for the content of NEFA and TG,and fatty acid synthase(FAS) expression was analyzed by Western blotting.After pretreatment with GEN for 30 min,3T3-L1 preadipocytes were stimulated with insulin for 5 or 10 min.The phosphorylation of p38 MAPK(p38) was analyzed by Western blotting.Results GEN inhibited lipid accumulation and decreased NEFA and TG content of 3T3-L1 on D 6 after the induction of differentiation.Pretreatment with GEN inhibited phosphorylation of p38 when stimulated with insulin.Furthermore,GEN inhibited the expression of FAS.SB203580,a p38 inhibitor,mimicked the FAS inhibition effect of genistein,which suggested that the inhibitory effect of GEN on FAS was partially via the p38 pathway.Conclusion Geinstein attenuates the differentiation of 3T3-L1 via the inhibition of p38 and FAS.