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Objective:To investigate the association between metabolic syndrome and the risk of early renal function injury in chronic kidney disease(CKD) in the elderly.Methods:A retrospective cohort was established based on health check-up data of 4 495 elderly residents in Mengzi City, Yunnan Province from January 2016 to December 2018. The medial history, living habits, and related physical examination information were collected. Cox hazard regression model was used to explore the association between metabolic syndrome, along with its components, and the early renal function injury in CKD. Results:The median age of the elderly was 71.00(67.00, 75.00) years, with metabolic syndrome detection rate of 21.98%. Early renal function injury of CKD developed in 1 300(28.92%) subjects during the follow-up. Univariate Cox regression showed that the number of metabolic syndrome components was associated with the risk of early kidney development in CKD. The HRs were 1.23 (95% CI 1.03-1.47, P=0.022) with 1 component, 1.54 (95% CI 1.28-1.84, P<0.001) with 2, and 1.38 (95% CI 1.14-1.67, P<0.001) with 3 or more. Multivariate Cox regression showed that elevated fasting triglycerides( HR=1.20, 95% CI 1.07-1.36, P=0.003) and lower high density lipoprotein-cholesterol(HDL-C; HR=1.25, 95% CI 1.09-1.43, P=0.002) were risk factors for early kidney injury in CKD, while doing some physical activity( HR=0.57, 95% CI 0.33-0.98, P=0.042), or on daily basis( HR=0.57, 95% CI 0.49-0.66, P<0.001) was a protective factor for early kidney injury in CKD. Conclusion:The abnormality of one or more metabolic components can significantly increase the risk of early kidney injury in the elderly with CKD. Elevated triglyceride and decreased HDL-C may be the risk factors.
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AIM:To observe the effect of rapamycin (Rapa) on human neuroblastoma SH-SY5Y cell injury induced by oxygen-glucose deprivation (OGD), and to explore the role of autophagy in this process .METHODS: The SH-SY5Y cells were randomly divided into 4 groups:normal control group:the cells were cultured without OGD treatment;Rapa group:the cells were pretreated with Rapa for 1 h;OGD group:the culture medium was replaced by glucose-free me-dium and the cells were transferred to a humidified incubation chamber flushed by a gas mixture of 1%O2 , 94%N2 and 5% CO2 for 12 h; Rapa+OGD group: the cultured cells were treated with Rapa for 1 h, and then were given the same treatments as those in OGD group .The cell viability was assessed by MTT assay .The degree of the cell damage was evalu-ated by determining the leakage of lactate dehydrogenase ( LDH) .The enzyme activity of caspase-3 was detected .TUNEL staining were used to detect the variation of cell apoptosis .The protein levels of apoptosis-related proteins Bax and Bcl-2, autophagy-related protein beclin-1 and autophagy marker protein LC 3B were determined by Western blot .RESULTS:Compared with OGD group, the viability of the SH-SY5Y cells was significantly increased, and the activity of caspase-3 was significantly reduced in Rapa +OGD group (P<0.05).The SH-SY5Y cell injury was apparent after OGD with a great in-crease in the apoptotic rate (P<0.05).Compared with OGD group, the apoptotic rate significantly decreased in Rapa +OGD group (P<0.05).Compared with control group, the protein level of Bcl-2 was significantly decreased (P<0.05) and the protein level of Bax was significantly increased in OGD group .Compared with OGD group , the levels of Bcl-2, be-clin-1 and LC3B-Ⅱwere significantly increased and the protein level of Bax was significantly increased in Rapa +OGD group (P<0.05).CONCLUSION: Rapamycin has a protective effect on in vitro cultured SH-SY5Y cells injured by OGD.The mechanism may be related to the promotion of autophagy .
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AIM: To examined the effects of hypoxic preconditioning ( HPC) on oxygen-glucose deprivation ( OGD)-induced PC12 cells, and to investigate its possible mechanisms of autophagy .METHODS: Cultured PC12 cells were randomly divided into control group , HPC group, 3-methyladenine (3-MA) group, HPC+OGD group, 3-MA+HPC+OGD group and OGD group .CCK-8 assay was used to detect the cell viability .The caspase-3 activity was also tested . TUNEL staining and flow cytometry were used to detect the cell apoptosis .The protein levels of apoptosis-related protein caspase-3 and autophagy-marked protein LC3-2 and beclin-1 were determined by Western blot .RESULTS:Compared with control group, the viability of PC12 cells was significantly reduced , and the activity of caspase-3 was significantly increased in OGD group.Compared with 3-MA+HPC+OGD group and OGD group , the viability of PC12 cells was significantly in-creased, and the activity of caspase-3 was significantly reduced in HPC +OGD group (P<0.05).The PC12 cell injury was apparent after OGD with a great increase in the apoptotic rate (P<0.05).Compared with OGD group, the apoptotic rate significantly decreased in HPC +OGD group ( P<0.05 ) .Compared with control group , the protein level of cleaved caspase-3 was significantly increased in OGD group ( P<0.05) .Compared with OGD group , the protein level of cleaved caspase-3 was significantly decreased , and the levels of LC3-2 and beclin-1 were significantly increased in HPC +OGD group (P<0.05).CONCLUSION:OGD decreases cell survival and induces apoptosis .Activation of cell autophagy may be the mechanism by which hypoxic preconditioning protects the PC 12 cells from OGD induced injury .
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Aim To investigate the protective effects of hydrogen sulfide ( H2 S) on focal cerebral ischemia/reperfusion injury in rats and the possible mechanisms. Methods Male Sprague Dawley rats were divided into three groups randomly: sham-operated group, cerebral ischemia/ reperfusion ( I/R) group and sodium hydro-sulfide ( NaHS ) + I/R group. The left temporary middle cerebral artery occlusion ( MCAO ) model was established by the line-embolism method. After rats were suffered 2h/24h ischemia/reperfusion stress, the mortality rate was evaluated, and the nervous function-al defect degree was evaluated by Longe scoring, the volumes of cerebral infarction was evaluated by 2 ,3 ,5-triphenyltetrazolium chloride ( TTC) staining, and the expression of P2X7 receptor protein in brain tissue was detected by the immunofluorescence method. Results The mortality rate in NaHS + I/R rats ( 29.41%) was obviously lower than those of I/R group ( 42 . 86%) . The nervous defect scores in NaHS + I/R rats were significant lower than those of I/R group ( P <0.05 ) . The volumes of cerebral infarction in NaHS +I/R group (21.88% ±3.53%) were significant lower than those of I/R group ( 36.71% ±3.73%) ( P <0.01 ) . The results of immunofluorescence showed that the positive expression cells of P2X7 receptor protein in cerebral cortex and hippocampal CA1 area of I/R group were significantly higher than those of sham-op-erated group(P<0. 01). However, compared with I/R group, the positive expression cells of P2X7 receptor protein in cerebral cortex and hippocampal CA1 area of NaHS + I/R group were significantly decreased ( P<0. 01). Conclusions H2S exerts the neuroprotective effect on focal cerebral ischemia/reperfusion injury in rats, and the protective mechanism might be associated with down-regulating the expression of P2X7 receptor protein in brain tissue.
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[ABSTRACT]AIM:ToexaminetheeffectsofhighconcentrationofextracellularATPonhumanneuroblastoma SH-SY5Y cell injury.METHODS: Cultured SH-SY5Y cells were grouped according to the concentrations of ATP and treatment time.The cell viability was detected by CCK-8 assay.The variation of autophagic vacuoles was observed with monodansylcadaverine staining .The cell apoptosis was analyzed by Hoechst 33258 staining.Meanwhile, apoptotic rate was detected by flow cytometry .The levels of caspase-3 and microtubule-associated protein 1 light chain 3-Ⅱ ( LC3-Ⅱ) were determined by Western blotting .RESULTS:Compared with control group , the survival rate of SH-SY5Y cells was signifi-cantly reduced by ATP at different concentrations (3, 6, 9, 12 and 15 mmol/L for 3 h) and different treatment time (1, 2, 3 and 6 h with 6 mmol/L ATP, peaking at 3 h).The autophagic vacuoles of SH-SY5Y cells were significantly increased at 1 h with ATP treatment , trended to decrease over time and returned to control level at 6 h.The protein expression of LC3-Ⅱwas significantly increased at 1 h with ATP treatment , which was consistent with the time points of increasing auto-phagic vacuoles .LC3-Ⅱexpression level gradually decreased at 2~3 h with ATP treatment , and returned to control level at 6 h.Compared with control group , the apoptotic rate and the expression level of caspase-3 were enhanced synchronously . The peak of apoptotic rate occurred at 3 h, and kept until 6 h.The level of cleaved caspase-3 expression peaked at 6 h. CONCLUSION:High concentration of extracellular ATP induces the autophagy and apoptosis of SH -SY5Y cells.The in-creased autophagy shows up , followed by the climax of apoptosis until 6 h.With the prolonged duration of ATP , apoptosis is the main process in the cells .
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Aim To explore the effects of clausenamide(Clau) on hippocampal heme oxygenase(HO-1 and HO-2) expressions in diabetic rats.Methods The diabetic rats model was produced by injecting streptozotocin (48 mg?kg-1). After 3 months,the HO-1 and HO-2 mRNA and protein expressions in hippocampus of diabetic rats were detected by RT-PCR and immunohistochemistry respectively.Results ① The results of RT-PCR showed that the protein expressions of HO-1 and HO-2 mRNA in hippocampus of diabetic group were higher than those of control group(P