ABSTRACT
AIM: To study the protective effect and mechanism of swimming on kidney of diabetic mice. METHODS: The mice were randomly divided into normal control group, normal swimming group, type 2 diabetes mellitus (T2DM) mice model group, diabetic swimming group and metformin group. T2DM model was established by streptozotocin (STZ) method. The mice in normal swimming group and diabetic swimming group were given swimming exercise (1 h a day), and the metformin group were given metformin (200 mg/kg) by gavage once a day for 7 weeks. Fasting blood glucose and serum insulin were measured and insulin resistance index was calculated. The contents of uric acid, urea and creatinine in serum were determined. The ratio of renal mass to body mass was calculated, and the pathological changes of renal tissues were observed. The relative expressions of autophagy related proteins LC3 and P62 in renal tissues were detected by Western blot. RESULTS: Compared with normal control group, insulin resistance index and renal mass/body mass ratio in model group were significantly increased. Serum uric acid, urea and creatinine levels increased, and glomerular pathological changes were obvious. LC3II/LC3I ratio decreased significantly. The expression of P62 was significantly increased. Compared with model group, insulin resistance index and renal mass/body mass ratio in diabetic swimming group were significantly decreased. The contents of serum uric acid, urea and creatinine decreased, and the pathological changes of glomerular were alleviated. LC3II/LC3I ratio increased significantly. The expression of P62 decreased significantly (P even <0.05). CONCLUSION: Swimming protects the kidney injury of T2DM mice, and its mechanism may be related to promoting the autophagy process of renal tissue.
ABSTRACT
Aim To explore the effect of receptor component protein(RCP)in the signal transduction of vascular smooth muscle cell(VSMC)proliferation induced by static pressure.Methods The mouse-derived vascular smooth muscle cell line(A10VSMC)was employed in the experiment.Cells were exposed to static pressure,and MTT assay was used to detect the cell viability.Western blot was used to determine the expressions of PCNA,RCP and p-Akt,RCP mRNA was tested by RT-PCR,and co-immunoprecipitation was used to test the interaction between RCP and G proteins.Results The cell viability,expressions of PCNA and RCP increased with the elevation of static pressure and reached their peaks at 120 mmHg,and after 6 hours they got a plateau.The static pressure significantly increased the level of p-Akt,meanwhile,the binding of RCP and Gαs significantly decreased.However,the binding of RCP and Gβ increased in response to static pressure after stimuli of static pressure,but Gγ was obscure.Conclusion Static pressure can induce VSMC proliferation and expression of RCP,which may involve G protein signal transduction model.
ABSTRACT
To investigate the effect of losartan on the axis of prolylcarboxypeptidase (PRCP)--kallikrein of the two-kidney, one-clipped (2K1C) hypertensives rats, and explore the novel protection mechanism of losartan on the kidney. Sprague-Dawley (SD) rats were used to develop the 2K1C hypertensive rats. Then, the rats were treated with prazosin (5 mg x kg(-1) x d(-1)) or losartan (5, 15 and 45 mg x kg(-1) x d(-1)) or vehicle, separately. At the same time, the blood pressures were observed. After treated for four weeks, the ratio of right kidney weight and body weight, the change of glomerular morphology, and K+, Na+, creatinine and blood urea nitrogen (BUN) of the serum were used for evaluation of kidney. The expressions of PRCP mRNA in the kidneys were determined by RT-PCR. The protein levels of PRCP, tissue kallikrein, plasma kallikrein, TGF-beta1 in kidney or plasma were measured by Western blotting. Results showed that the changes of body weight and kidney weight ratio, glomerular fibrosis degree and the biochemistrical index of serum induced by hypertension were relieved when the hypertensive rats treated with losartan for four weeks. Meanwhile, treatment of losartan also significantly decreased expression of TGF-beta1 and increased expressions of PRCP, plasma kallikrein and tissue kallikrein. The protective effects of losartan on the kidney of 2K1C hypertensive rats are activation of the axis of PRCP-kallikrein and reducing the expression of TGF-beta1.
ABSTRACT
This study is to investigate the impairment and possible mechanism of endothelium-dependent relaxation of mice mesenteric arteries induced by mmLDL. Wire myography was employed to examine endothelial function of mesenteric arteries. Ultramicrostructure of mesenteric vascular beds were detected by transmission electron microscope. The results showed that endothelium cell edema and peeling, vascular elastic membrane fracture traces in mmLDL group. Endothelium-dependent relaxation was decreased in a time-dependent and dose-dependent manner by using mmLDL, compared with normal arteries. In endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation, the Rmax and pIC50 were decreased from (63 +/- 5) % and 6.42 +/- 0.09 of normal saline control to (31 +/- 3) % and 5.67 +/- 0.07 in mmLDL group (P < 0.001, P < 0.001), respectively. In nitric oxide (NO)-mediated relaxation, the Rmax and pIC50 were decreased from (45 +/- 4) % and 5.93 +/- 0.08 in normal saline control to (32 +/- 4) % and 5.43 +/- 0.11 in mmLDL group (P < 0.05, P < 0.01), respectively. There is no significant alteration of prostacyclin I2 (PGI2) pathway between these two groups. In conclusion, mmLDL induced the impairment of the ultramicrostructure of mesenteric vascular endothelium cell as well as the endothelium-dependent relaxation. The latter includes the dysfunction of NO- and EDHF pathway mediated endothelium-dependent relaxation.
ABSTRACT
AIM: To elucidate the effects of losartan on the expression ofmatrix metalloproteinases-2, JNK1/2 and proliferation in cardiac fibroblast. METHODS: Neonatal rat cardiac fibroblasts were cultured. The cells proliferation was determined by MTT. To determine effects of AngⅡ on JNK1/2 activity, cells were incubated (for 0, 2, 5, 10, 30, 60, 120 min) in serum-freemedia with AngⅡ, and the other group fibroblasts were exposed to serum-free media with or without AngⅡ and losartan (AngⅡ 100 nmol/L, AngⅡ 100 nmol/L+losartan 100 nmol/L, losartan100 nmol/L, losartan for 45 min before). Cells protein was collected with MBST buffer. The relative abundance of MMP-2, JNK1/2 and p-JNK1/2 in cells was determined by immunoblotting. The secretion of MMP-2 in media of cell culture was determined by ELISA. RESULTS: AngⅡ increased the proliferation of CFB in a dose-dependent manner, whereas losartan decreased the proliferation of CFB stimulated by AngⅡ in a dose-dependant manner, too (P＜0.05). The relative abundance of JNK1/2 was highest in AngⅡ of the 2-min-stimulated group. AngⅡincreased expression of JNK1/2 and MMP-2 protein (P＜0.05), on the contrary, losartan inhibited JNK1/2 and MMP-2 protein expression.CONCLUSION: AngⅡ induce the increase of proliferation of CFB, expression of JNK1/2 and MMP-2 in CFB, and losartan inhibits these effects of AngⅡ.
ABSTRACT
Objective To investigate the effect of angiotensin Ⅱ-1 receptor antagonist losartan on expression of tumor necrosis factor-alpha (TNF-?) in the ventricular myocardium in the renovascular hypertension rats. Methods Renovascular hypertension model was obtained by clip left renal artery in Sprague-Dawley(SD) rats. After operation the rats were divided into 3 groups: sham group, two-kidney one clip (2K1C) group, and losartan treatment group(2K1C and losartan 20 mg/kg?d by drinking). Tail blood pressure was determined every week. Animals were euthanized after treatment with losartan for four weeks. Cardiac index(CI)was calculated by HW/BW, and TNF-? protein of ventricle myocardium was determined by ELISA and immunohistochemistry. Results Losartan significantly decreased blood pressure(P
ABSTRACT
Aim To study the effect of Macrophage colony-stimulating factor(M-CSF) on MMP-9 in RAW 264.7 cell and explore the relationship between atherosclerosis caused by M-CSF and the activity of MMP-9. Methods Gelatin zymography analysis was used to investigate the effect of M-CSF and PD98059 on the activity of MMP-9 in cultured RAW 264.7 cell.Western blot was used to study the effect of M-CSF and PD98059 on the express of p-ERK1/2 in cultured RAW 264.7 cell. Results The enzyme activity of MMP-9 was significantly increased after 24-hour M-CSF treatment.Meanwhile, M-CSF upregulated the expression of p-ERK1/2. Pre-treatment with PD98059 blocked partly the increased expression of p-ERK1/2 and the activity of MMP-9 induced by M-CSF. Conclusion M-CSF can induce the secretion of MMP9 in RAW 264.7 cell, which may be mediated by the phosphorylation of ERK1/2.
ABSTRACT
Aim To compare the effects of the non-peptide angiotensin Ⅱ receptor type Ⅰ antagonist,Losartan,and the active vascular peptide,calcitonin gene-related peptide(CGRP),on the proliferation of vascular smooth muscle cells induced by angiotensin Ⅱ,and to explore the mechanism of depressor effect of Losartan and CGRP in vivo.Methods MTT,Thymidine incorporation and flow cytometry,were used to determine the ability of proliferation of VSMC induced by angiotensin Ⅱ in the presence or absence of Losartan or CGRP,Western blotting was used to determine the activity of ERK1/2.Results Losartan or CGRP inhibited the viability,DNA synthesis,cell proliferation index,and the activity of ERK1/2 in a dose-dependent manner.Conclusion Losartan or CGRP significantly inhibits the proliferation of VSMC induced by angiotensin Ⅱ;the inhibitory effect of CGRP is stronger than that of Losartan.The signaling path way is involved in ERK1/2.