[Investigation on the Influencing Factors of Adult Dyslipidemia in Shunqing District of Nanchong City].

OBJECTIVE: To analyze the risk factors of dyslipidemia of adult residents in Shunqing District of Nanchong City. METHODS: A five-stage stratified cluster sampling method was used to select adult residents from 9 communities in the urban area of Shunqing District of Nanchong City from January 2013 to April 2018 for questionnaires survey,physical measurement and laboratory test. Univariate analysis and multivariate logistic regression analysis were used to study the influencing factors of dyslipidemia. RESULTS: A total of 105 956 people was investigated,and the prevalence rate of dyslipidemia was 34.2% (36 272 cases). Among them, the prevalence rate of male was 38.11%, and 31.91% for female ( P<0.01). The proportion of dyslipidemia with hypertension, diabetes, and coronary heart disease was 13.46%, 5.74%, and 0.39%, respectively. The proportion of hypertension with diabetes was 2.79%. Multivariate logistic regression analysis showed that gender (odds ratio ( OR)=1.276, P<0.001), body mass index ( OR=1.052, P<0.001), education level (set ≤elementary school as reference, high school OR=1.094, P<0.001, ≥graduated OR=1.185, P<0.001), smoking history ( OR=1.124, P<0.001), coronary heart disease ( OR=1.189, P<0.001), hypertension ( OR=1.148, P<0.001),sdiabetes ( OR=1.967, P<0.001), and family history of dyslipidemia ( OR=1.760, P<0.001) were the influencing factors of dyslipidemia in residents of this region. Conclusions The dyslipidemia of urban residents in Nanchong area is highly concerned with hypertension, diabetes, and coronary heart disease. Male, obesity, high education level, smoking, coronary heart disease, hypertension, diabetes, and family history of dyslipidemia are risk factors for dyslipidemia in urban residents of Nanchong area. It is necessary to actively target the above risk factors and high-risk groups.

CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells.

While Helicobacter pylori (Hp) infection is closely associated with IgA nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a major virulence factor of Hp, on the production and underglycosylation of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with recombinant CagA protein. We found that CagA stimulated cell proliferation and the production of IgA1 in a dose-dependent and time-dependent manner. Moreover, CagA promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of ß1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN by influencing the production and glycosylation of IgA1 in B cells.

Ginsenoside Rg1 modulation on thrombospondin-1 and vascular endothelial growth factor expression in early renal fibrogenesis in unilateral obstruction.

Renal interstitial fibrosis is the major histopathological change seen in a variety of renal disorders and is closely related to renal dysfunction. Progressive interstitial fibrosis accompanied by the loss of renal tubules and interstitial capillaries typifies all progressive renal disease. Thrombospondin-1 (TSP-1) is a major angiogenic inhibitor. It is demonstrated that TSP-1 levels were correlated with the loss of glomerular and peritubular capillaries and TSP-1 could promote renal scarring by effects on the endothelium. It has been reported that ginsenoside Rg1 inhibited renal interstitial fibrosis in rats via suppressing the expression of TSP-1. The present study was designed to examine whether ginsenoside Rg1 could modulate the integrity of the microvasculature and hence affect the progression of renal fibrosis in a rat unilateral ureteral obstruction (UUO) model. In UUO control kidneys, associated with interstitial fibrosis, lower peritubular capillary densities were prominent. These changes were all improved by ginsenoside Rg1 treatment. Interestingly, ginsenoside Rg1 decreased the expression of TSP-1 and enhanced vascular endothelial growth factor (VEGF) expression. The results show for the first time that ginsenoside Rg1 can evidently inhibit renal interstitial fibrosis in rats with UUO. The mechanism might be related to suppression of the expression of TSP-1 and to repair of the peritubular capillary.

[Leukemia inhibitory factor suppresses renal interstitial fibroblast activation induced by transforming growth factor].

OBJECTIVE: To investigate the effects of leukemia inhibitory factor (LIF) on renal interstitial fibroblast activation following induction by transforming growth factor beta 1 (TGF-beta1). METHODS: Normal rat interstitial fibroblast cells (NRK/49F) were treated with TGF-beta1 and TGF-beta1, combining with LIF respectively for different duration with different concentration. Changes in cell morphology and expression of alpha-SMA were evaluated with electronic microscope and Western blot respectively. The collagen I in the supernatant was detected with ABC-ELISA. RESULTS: TGF-beta1 induced renal interstitial fibroblast activation, and this was accompanied by significant morphological transformations and secretion of collagen I. Co-culturing of cells with LIF blocked the morphological transformation. In addition, LIF inhibited TGF-beta1-induced expression of alpha-SMA mRNA and protein (P < 0.01), and decreased the levels of collagen I (P < 0.01) in a dose-dependent manner. CONCLUSION: LIF suppresses TGF-beta1-induced activation and collagen I secretion of cultured renal interstitial fibroblasts.

[Effects of salidroside on tubular epithelial to myofibroblast transition under cobaltous chloride induced hypoxic status].

OBJECTIVE: To investigate the effect and possible mechanism of salidroside on the transdifferentiation of normal rat kidney tubular epithelia cells (NRK52E) under cobaltous chloride (Co) induced hypoxic status. METHODS: Cultured NRK52E cells were divided into control group, Co group and Co plus salidroside treatment groups at a dosage of 10 micromol/L, 50 micromol/L, and 100 micromol/L. Hypoxia-inducible factor-1alpha (HIF-1alpha), a master regulator of oxygen homeostasis was measured as a marker of hypoxic status. Morphologic alteration of cells was observed by inverted phase contrast microscope. The expression of alpha-SMA in NRK52E cells was detected by fluorescent immunocytochemistry (FICC) and immunohistochemistry (IHC). The alpha-SMA and TGF-beta1 mRNA were assessed using reverse transcription-polymerase chain reaction (RT-PCR). The expressions of HIF-1alpha and alpha-SMA protein were detected by Western blot analyses. The enzyme-linked immunosorbent assay was performed to detect collagen I (Col-I) and fibronectin (FN) in the supernatant. RESULTS: The expression of HIF-1alpha in NRK52E cells was induced by 100 micromol/L of Co in vitro. Co induced transdifferentiation of NRK52E cells, showing fibroblast-like in morphology. Salidroside partly blocked morphologic transformation of tubular epithelial cells. Salidroside decreased the expressions of alpha-SMA protein and mRNA and TGF-beta1 mRNA significantly (P < 0.05), although they were still higher than the controls (P <0 .05). Salidroside, especially in high dosage, inhibited the increase in Col-I and FN induced by Co (P < 0.05). CONCLUSION: Hypoxia can induce tubular epithelial-myofibroblast transdifferentiation (TEMT). Salidroside improves Co-induced hypoxic status and inhibits TEMT possibly through reducing Col I and FN in NRK52E cells.

LSKL, a peptide antagonist of thrombospondin-1, attenuates renal interstitial fibrosis in rats with unilateral ureteral obstruction.

The effects of LSKL, the peptide antagonist of thrombospondin-1 (TSP-1), on renal interstitial fibrosis in rats subjected to unilateral ureteral obstruction (UUO) were investigated. Rats were divided randomly into three groups (n = 20 each): UUO group, sham-operation group and UUO plus LSKL treatment group. Collagen deposition was studied using histopathology and reverse transcription polymerase chain reaction analysis (RT-PCR). TSP-1, transforming growth factor beta 1 (TGF-beta1), phosphorylated Smad2 (pSsmad2) and alpha-smooth muscle actin (alpha-SMA) in the kidney were measured using immunocytochemistry, western blotting analysis, RT-PCR and enzyme-linked immunosorbent assay. Biochemical analyses in the serum and urine were made. Histopathology showed severe tubular dilatation and atrophy, interstitial inflammation and collagen accumulation after surgery and LSKL significantly inhibited interstitial fibrosis including tubular injury as well as collagen deposition. The protein and mRNA levels of TSP-1 increased notably at different time point and significantly decreased in the presence of LSKL. The expression of TGF-beta1 and pSmad2 were upregulated in the obstructed kidney and substantially suppressed by LSKL treatment. Myofibroblast accumulation could be alleviated after administration of LSKL. Biochemical parameters did not show differences among the three groups. As TSP-1 is the major activator of TGF-beta1, we demonstrate that LSKL can attenuate renal interstitial fibrosis in vivo by preventing TSP-1-mediated TGF-beta1 activation.

Hydraulic pressure inducing renal tubular epithelial-myofibroblast transdifferentiation in vitro.

OBJECTIVE: The effects of hydraulic pressure on renal tubular epithelial-myofibroblast transdifferentiation (TEMT) were investigated. METHODS: We applied hydraulic pressure (50 cm H2O) to normal rat kidney tubular epithelial cells (NRK52E) for different durations. Furthermore, different pressure magnitudes were applied to cells. The morphology, cytoskeleton, and expression of myofibroblastic marker protein and transforming growth factor-beta1 (TGF-beta1) of NRK52E cells were examined. RESULTS: Disorganized actin filaments and formation of curling clusters in actin were seen in the cytoplasm of pressurized cells. We verified that de novo expression of alpha-smooth muscle actin induced by pressure, which indicated TEMT, was dependent on both the magnitude and duration of pressure. TGF-beta1 expression was significantly upregulated under certain conditions, which implies that the induction of TEMT by hydraulic pressure is related with TGF-beta1. CONCLUSION: We illustrate for the first time that hydraulic pressure can induce TEMT in a pressure magnitude- and duration-dependent manner, and that this TEMT is accompanied by TGF-beta1 secretion.

[Effect of ginsenoside Rgl on the expression of TNF-alpha and MCP-1 in rats with diabetic nephropathy].

OBJECTIVE: To investigate the effects of Ginsenoside Rgl on proteinuria and the expression of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) in rats with diabetic nephropathy (DN). METHODS: The DN rat model was established by injection of streptozotocin (STZ, 65 mg/kg) in abdominal cavity. Forty Sprague-Dawley male rats were randomly divided into 4 groups: normal group, DN group, Ginsenoside Rgl treatment group and Irbesartan treatment group. The blood glucose was monitored routinely. Twenty-four hours urine protein and serum creatine were measured the day before the rats were killed when the eight weeks of treatments had been completed. The renal pathological and podocyte changes were evaluated. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were performed to examine the protein expression levels of MCP-1 and TNF-alpha, respectively. The mRNA of TNF-alpha and MCP-1 were reverse transcribed and quantified by real-time PCR. RESULTS: The DN rats had increased volume of renal glomerulus, thickened basement membrane, and increased mesenterium mass, as well as some inflammatory cells in renal glomerulus. The number of potocyte decreased significantly in the DN group compared with the normal group (P<0.01). Compared with the DN group, the basement membrane became thinning and the number of podocyte increased in the two treatment groups (P<0.05). The rats in the DN group and the two treatment groups had significantly higher levels of twenty-four hour urine protein, serum creatine, serum glucose, serum MCP-1 and TNF-alpha than the normal rats (P<0.05). The rats in the treatment groups had lower levels of twenty-four hours urine protein and serum creatine than the rats in the DN group (P<0.05). But the serum glucose had little changes (P>0.05). There was no difference between the two treatment groups. Immunohistochemisty, ELISA and real-time PCR results indicated that the expression levels of MCP-1 and TNF-alpha in the rats in the DN group and the two treatment groups were significantly higher than those in the normal group (P<0.05). The rats in the treatment groups had lower levels of expression of MCP-1 and TNF-alpha than those in the DN group (P<0.05). The correlation analysis indicated that the levels of MCP-1 and TNF-alpha were positively related to twenty-four hours urine protein (r=0.7802, 0.6963), glomerular sclerosis index (r=0.8296, 0.7413) and thickness of podocyte membrane (r=0.7678, 0.6701, P<0.05). CONCLUSION: Ginsenoside Rgl reduces the expression of MCP-1 and TNF-alpha, repairs the pathological lesions of podocyte and nephron, and reduces the twenty-four hour urine protein rats with diabetic nephropathy.

Ginsenoside Rb1, a panoxadiol saponin against oxidative damage and renal interstitial fibrosis in rats with unilateral ureteral obstruction.

OBJECTIVE: To investigate the possible protective effect and mechanism of ginsenoside Rb1 against oxidative damage and renal interstitial fibrosis on rats with unilateral ureteral obstruction (UUO). METHODS: In total, 80 male rats were randomly divided into 4 groups, 20 in each group: the sham operated group (SOR), UUO group, UUO with ginsenoside Rb1 treatment group (treated with intraperitoneal injection of 50 mg/ kg daily) and UUO with Losartan treatment group (as the positive control, treated with 20 mg/kg by gastrogavage per day). The rats were randomly sacrificed on day 3, 7 and 14 after surgery, respectively. The histopathologic changes of renal interstitial tissues were observed with Masson staining. The mRNA of transforming growth factor beta 1 (TGF-beta 1), collagen I and fibronectin were reversed transcribed and quantified by Real-time PCR. Enzyme-linked immunosorbent assay was used to quantitatively detect TGF-beta 1 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. P47phox protein expression was assessed by immunohistochemistry and Western blot analysis. RESULTS: In the UUO model, the obstructed kidney showed typical features of progressive renal tubulointerstitial fibrosis, and the levels of TGF-beta1, collagen I and fibronectin increased (P<0.05). As compared with the UUO group, ginsennoside Rb1 significantly inhibited the interstitial fibrosis including tubular injury and collagen deposition, and decreased the levels of TGF-beta1 (P<0.05). Ginsenoside Rb1 also inhibited the heme oxygenase (HO-1) and 8-OHdG, two markers of oxidative stress (P<0.05). Moreover, ginsenoside Rb1 suppressed the expression of p47phox, a subunit of nicotinamide adeninedinucleotide phosphate (NADPH) oxidase (P<0.05). CONCLUSION: Ginsenoside Rb1 can obviously inhibit renal interstitial fibrosis in rats with UUO, its mechanism possibly via against the oxidative damage and suppressing TGF-beta1 expression.

[Effect of Astragalus mongholicus on expression of hepatocyte growth factor in SD rats with unilateral ureteral obstruction].

OBJECTIVE: To study the effect of Astragalus mongholicus (AM) on the expression of hepatocyte growth factor (HGF) in SD rats with unilateral ureteral obstruction (UUO) and to elucidate the mechanisms underlying the renoprotective effects of AM. METHODS: Fifty four Sprague-Dawley rats were randomly divided into 3 groups: sham-operation group (SOR), UUO group (UUO) and UUO + AM group (AM). After administration of AM[10 g/ (kg x d)] for 3, 7 and 14 days,the histological changes of renal interstitial tissues were observed dynamically, and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The protein expression of HGF and alpha-smooth muscle actin (alpha-SMA) was measured by immunohistochemistry. The mRNA expression of HGF and alpha-SMA were determined by real-time PCR. The expression of HGF and its receptor (C-met) were assessed by Western blot. RESULTS: Renal damage was exacerbated and the expression of alpha-SMA was significantly increased in UUO group compared with those of SOR group (P < 0.05) at each time point. HGF and C-met expression peaked at the 7th day after UUO and then decreased greatly. After AM intervention, tubular impairment and interstitial fibrosis were alleviated, up-regulations of alpha-SMA expressions was significantly suppressed, whileas the expression of HGF and C-met were significantly increased when compared with UUO group (P < 0. 05) at each time point. CONCLUSION: AM can ameliorate renal interstitial fibrosis induced by UUO in rats. The mechanisms of its antifibrotic effects may be related with the up-regulation of HGF and C-met expression, and the suppression of tubulo-epithelial mesenchymal transdifferentiation in renal intersitial progress.

[Effects of ginsenoside Rb1 on TGF-beta1 induced p47phox expression and extracellular matrix accumulation in rat renal tubular epethelial cells].

OBJECTIVE: To investigate the effects of Ginsenoside Rb1 (G-Rb1) on the oxidative damage and extracellular matrix accumulation in rat renal tubular epethelial cells induced by transforming growth factor-beta1 (TGF-beta1). METHODS: Cultured normal rat renal tubular epethelial cells (NRK-52E) were divided into control group, 10 ng/mL TGF-beta1-induced group, G-Rb1 treated groups in which rat renal tubular epethelial cells were treated with different concentration of G-Rb1 (10 ng/mL, 20 ng/mL, 40 ng/mL) after TGF-beta1 induction, G-Rb1 40 ng/mL group and 100 nmol/L DPI(diphenyleneiodonium, an inhibitor of NADPH oxidase) group. Intracellular reactive oxidative species (ROS) level was measured by flowcytometry. p47phox protein expression was assessed by immunohistochemistry and western blotting method. The expressions of collagen I (Col-I) and fibronectin(FN) gene were measured by real-time PCR analysis. The protein level of Col-I and FN were quantitatively detected by enzyme-linked immunosorbent assay. RESULTS: TGF-beta1 at 10 ng/mL significantly increased the intercellular ROS production and p47phox expression (P < 0.05). The levels of Col-I and FN were also significantly up-regulated with the stimulation of 10 ng/mL TGF-beta1 (P < 0.05). Compared to TGF-beta1-induced group, G-Rb1 and DPI depressed TGF-beta1-induced ROS production and p47phox overexpression. Meanhile, G-Rb1 and DPI decreased the levels of Col-I and FN. CONCLUSION: G-Rb1 could inhibit TGF-beta1 induced ROS production and decrease the levels of Col-I and FN in a dose-dependent manner. The mechanism might be partly related to the suppression of p47phox expression.

Ginsenoside Rg1, a major active component isolated from Panax notoginseng, restrains tubular epithelial to myofibroblast transition in vitro.

The medicinal herb, Panax notoginseng, has been used for thousands of years in traditional Chinese medicine and possesses anti-fibrosis properties. Epithelial-myofibroblast transition (EMT) plays an important role in renal tubulointerstitial fibrosis. The present study was designed to examine whether ginsenoside Rg1, a major active component isolated from Panax notoginseng, has an ability to block this phenotypic transition in rat renal tubular epithelial cells (NRK-52E) induced by transforming growth factor-beta1 (TGF-beta1). The morphology of tubular epithelial-myofibroblast transition was observed through light microscope and transmission electron microscopy. alpha-SMA and E-cadherin are two markers of tubular epithelial-myofibroblast transition, their protein expressions were assessed by immunohistochemistry and western blot analysis. Gene expression of alpha-SMA as well as the two major extracellular matrix components collagen I and fibronectin was measured by real-time PCR analysis. Enzyme-linked immunosorbent assay was used to quantitatively detect collagen I and fibronectin in the supernatant. Our results revealed that ginsenoside Rg1 obviously blocked morphologic transformation in NRK-52E induced by TGF-beta1. Meanwhile, ginsenoside Rg1 inhibited the expression of alpha-SMA and the loss of E-cadherin, subsequently decreased the levels of collagen I and fibronectin in a dose-dependent manner. In addition, western blot analysis indicated that ginsenoside Rg1 inhibited the expression of P-ERK1/2 in NRK-52E induced by TGF-beta1. These results suggest that ginsenoside Rg1 can restrain the process of EMT maybe via suppressing the expression of P-ERK1/2 in vitro.

[Ginsenoside R(g1) inhibit transdifferentiation in rat renal tubular epethelial cells induced by TGF-beta1].

OBJECTIVE: To investigate the effects of ginsenoside R(g1) on the transdifferentiation of rat renal tubular epethelial cells induced by transforming growth factor-beta1, (TGF-beta1). METHOD: Cultured normal rat renal tubular epethelial cells (NRK-52E) were divided into control group, TGF-beta1-induced group and treated with ginsenoside R(g1) at different concentration (10, 20, 40 mg x L(-1)) group. The morphology of tubular epithelial-myofibroblast transdifferentiation induced by TGF-beta1 was observed through light microscope. alpha-SMA and E-cadherin protein expression were assessed by immunohistochemistry and western blot analyses. alpha-SMA, collagen I and and fibronectin gene expression were assessed by real-time quantitative chain reaction. Enzyme-linked immunosorbent assay was used to quantitatively detect collagen I and fibronectin in the supernatant. RESULT: 10 mg x L(-1) TGF-beta1 could induce the transdifferentiation of tubular epithelial myofibroblast, showing fibroblast-like in morphology, with significantly enhanced expression of alpha-SMA, depressed expression of E-cadherin and increased secretion of fibronectin and collagen I (P < 0.05). Compared to TGF-beta1-induced group, ginsenoside R(g1) partly abrogated the alpha-SMA expression and E-cadherin depression triggered by TGF-beta1 in tubular epithelial cells in a dose-dependent manner (P < 0.05). Meanhile, ginsenoside R(g1) blocked morphologic transformation of tubular epithelial cells and decreased levels of collagen I and fibronectin (P < 0.05). CONCLUSION: Ginsenoside R(g1) could inhibit TGF-beta1 induced the tubular epithelial-myofibroblast transdifferentiation and decreased levels of collagen I and fibronectin in NRK52E.

Influence of ginsenoside Rg1, a panaxatriol saponin from Panax notoginseng, on renal fibrosis in rats with unilateral ureteral obstruction.

Total saponins of Panax notoginseng (PNS) have been shown to ameliorate renal interstitial fibrosis. Ginsenoside Rg1, a panaxatriol saponin, is one of the major active molecules from PNS. The present study was undertaken to investigate the effect of ginsenoside Rg1 on renal fibrosis in rats with unilateral ureteral obstruction (UUO). The rats were randomly divided into 3 groups: sham-operation (n=15), UUO (n=15) and UUO with ginsenoside Rg1 treatment (n=15, 50 mg per kg body weight, intraperitoneally (i.p.) injected). The rats were sacrificed on Days 7 and 14 after the surgery. Histological examination demonstrated that ginsenoside Rg1 significantly inhibited interstitial fibrosis including tubular injury as well as collagen deposition. alpha-smooth muscle actin (alpha-SMA) and E-cadherin are two markers of tubular epithelial-myofibroblast transition (TEMT). Interestingly, ginsenoside Rg1 notably decreased alpha-SMA expression and simultaneously enhanced E-cadherin expression. The messenger RNA (mRNA) of transforming growth factor-beta1 (TGF-beta1), a key mediator to regulate TEMT, in the obstructed kidney increased dramatically, but was found to decrease significantly after administration of ginsenoside Rg1. Further study showed that ginsenoside Rg1 considerably decreased the levels of both active TGF-beta1 and phosphorylated Smad2 (pSmad2). Moreover, ginsenoside Rg1 substantially suppressed the expression of thrombospondin-1 (TSP-1), a cytokine which can promote the transcription of TGF-beta1 mRNA and the activation of latent TGF-beta1. These results suggest that ginsenoside Rg1 inhibits renal interstitial fibrosis in rats with UUO. The mechanism might be partly related to the blocking of TEMT via suppressing the expression of TSP-1.