ABSTRACT
ObjectiveTo observe the effect of modified Da Chaihutang on cholesterol gallstone （CS） in mice due to damp-heat based on the farnesoid X receptor （FXR）/fibroblast growth factor 15 （FGF15）/fibroblast growth factor receptor 4 （FGFR4） pathway and explore the molecular biological mechanisms of CS differentiated into damp-heat syndrome from the perspective of correspondence between prescription and syndrome. MethodForty-eight six-week-old mice were randomly divided into the blank group， model group， modified Da Chaihutang （23.4 g·kg-1） group， and ursodeoxycholic acid （0.12 g·kg-1） group， with 12 mice in each group. The ones in the latter three groups were exposed to "internal dampness + external dampness + high-cholesterol diet" for 12 weeks for inducing CS due to damp-heat. Mice in the modified Da Chaihutang group and ursodeoxycholic acid group were gavaged with the corresponding drugs， while those in the model and blank groups with the same amount of normal saline for a total of four weeks. Before and after modeling， mice in each group were subjected to open field tests for determining their activities and mental states. Such general conditions as body mass， food intake， fur， and urine and stool of mice in each group were observed and recorded weekly for judging the damp-heat syndrome. After the intervention， the sampled liver and gallbladder tissues of mice in each group were stained with hematoxylin-eosin （HE） staining， and the serum γ-glutamyltransferase （GGT）， alkaline phosphatase （ALP）， and total bilirubin （TBIL） were determined. The total cholesterol （TC） and total bile acid （TBA） contents in bile were measured by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of FXR， FGF15， FGFR4， and cholesterol 7α-hydroxylase gene （CYP7A1） were assayed by real-time fluorescence quantitative polynucleotide chain reaction （Real-time PCR） and Western blot. ResultCompared with the blank group， the model group exhibited enlarged gallbladder， brown turbid bile with flocculent precipitation visible to the naked eye， obvious damp-heat syndrome， lipoid degeneration in the liver tissue， rough and thickened gallbladder wall， elevated ALP， GGT， and TBIL in serum （P<0.01） and TC in bile （P<0.01）， reduced TBA （P<0.01）， up-regulated FXR， FGF15， and FGFR4 mRNA and protein expression in ileum （P<0.05， P<0.01）， and down-regulated CYP7A1 mRNA and protein expression （P<0.01）. Compared with the model group， the two medication groups displayed improved bile turbidity， and the bile in the modified Da Chaihutang group became clearer. After intervention， the damp-heat syndrome of mice in the modified Da Chaihutang group was significantly alleviated. The liver and gallbladder lesions of mice in the two medication groups were significantly relieved， manifested as reduced serum ALP， GGT， and TBIL （P<0.01）. The reduction in ALP and TBIL of the modified Da Chaihutang group was more significant （P<0.01）. The TC contents in the bile of mice from the two medication groups were significantly lowered， whereas the TBA contents were elevated （P<0.01）， with more significant changes present in the modified Da Chaihutang group （P<0.01）. The mRNA and protein expression levels of FXR， FGF15， and FGFR4 in the modified Da Chaihutang group were down-regulated （P<0.05， P<0.01）， while the mRNA and protein expression levels of CYP7A1 rose （P<0.05）， except that the elevation in FGF15 and FGFR4 protein expression and reduction in CYP7A1 protein expression were not significant. The mRNA and protein expression levels of FXR， FGF15， and FGFR4 in the ursodeoxycholic acid group all decreased， among which the reduction in FXR was remarkable （P<0.05）， and the mRNA and protein expression levels of CYP7A1 were significantly up-regulated （P<0.05）. ConclusionModified Da Chaihutang significantly improves the stone， liver function， bile composition， abnormal cholesterol-bile acid metabolism， and damp-heat syndrome in the model mice of CS differentiated into damp-heat syndrome， which may be related to its regulation of key factors FXR， FGF15， FGFR4， and CYP7A1 mRNA and protein expression in the cholesterol-bile acid metabolism pathway.
ABSTRACT
Objective To study the effects of different hemodialysis modes on growth factor-15 (GDF-15) and left ventricular function in uremic patients undergoing maintenance hemodialysis (MHD). Methods One hundred and twenty uremic patients with chronic renal failure whose MHD > 3 months admitted to Guiyang Second People's Hospital from June 2017 to June 2018 were enrolled, and they were divided into a hemodialysis (HD)+ hemofiltration (HDF)+hemoperfusion (HP) group (HD 8 times per month, HDF 4 times per month, HP 1 time per month), a HD+HDF group (HD 8 times per month, HDF 1 time per month) and a HD group (HD 8 times a month) according to different dialysis modes, each group 40 cases. The patients' venous blood was collected before treatment and 6 months and 1 year after treatment, serum was separated, and the GDF-15 levels in the three groups were detected; the left ventricular end-diastolic dimension (LVDD), left ventricular end-systolic dimension (LVDS), left ventricular end-diastolic volume (LVVD), left ventricular end-systolic volume (LVVS), left ventricular posterior wall thickness (LVPWT), ventricular septal thickness (LVST), maximum blood flow ratio (E/A) of early to late diastole and left ventricular ejection fraction (LVEF) in three groups were detected by echocardiography. Results After treatment, the GDF-15 levels and LVDD, LVDS, LVVD, LVVS, LVPWT, LVST and E/A in the three groups were significantly lower than those before treatment, while LVEF was significantly higher than that before treatment (all P < 0.05); the changes after treatment in the HD+HDF+HP group were more significant than those in the HD+HDF group and HD group [GDF-15 (ng): 853.78±78.80 vs. 921.73±72.54, 971.07±72.05, LVDD (mm): 48.25±1.25 vs. 50.67±1.26, 51.69±1.33, LVDS (mm): 35.21±1.01 vs. 37.84±0.90, 38.91±0.83, LVVD (mL): 101.44±4.40 vs. 109.27±6.47, 115.11±5.46, LVVS (mL): 35.75±1.52 vs. 37.75±1.70, 39.48±1.48, LVPWT (mm): 8.26±0.77 vs. 10.24±0.98, 11.22±0.91, LVST (mm): 9.07±0.48 vs. 10.47±0.61, 11.60±0.58, E/A: 1.03±0.05 vs. 1.07±0.06, 1.15±0.08, LVEF: 0.64±0.03 vs. 0.59±0.03, 0.51±0.04, all P <0.05]. Conclusion The combined hemo- dialysis with different hemodialysis modes can effectively reduce the level of GDF-15 in uremic patients with chronic renal failure and MHD and improve their left ventricular function, thus the incidence of cardiovascular events and mortality in such patients can be decreased.
ABSTRACT
Objective To investigate the level of plasma GDF-15 in patients with COPD and its clinical value in the diagnosis of COPD in the stable stage and in acute exacerbation stage. Methods From 2015 to 2016, 58 cases of patients with COPD were enrolled ,including COPD patients in the stable stage and in acute exacerba-tion stage. 29 cases of COPD patients diagnosed in our hospital were enrolled in the experimental group ,and 29 cases of age-,gender and body mass index-matched healthy people were enrolled in the control group. Compared and analyzed the blood cell count ,determination of plasma GDF-15 and C-reactive protein were performed and ana-lyzed. Spearman correlation analysis was conducted to compare levels of GDF-15 and C-reactive protein between pa-tients with the stable stage of COPD and those with acute exacerbation stage of COPD. The diagnostic efficacy was compared between GDF-15 and C-reactive protein in differentiatingthe COPD in acute exacerbation period and in the stable period. Results Level of GDF-15 in the stable COPD patients was significantly increased compared with that in the control group. The plasma GDF-15 level was significantly increased in acute exacerbation COPD patients compared to patient with the stable COPD(P<0.001). For the stable COPD patients,GDF-15 level and C-reactive protein level was positively correlated(r = 0.776,P < 0.001). In acute exacerbation COPD patients, GDF-15 level and C-reactive protein level was positively correlated (r = 0.877,P < 0.001). The ROC curves showed that the GDF-15 level on the diagnosis of acute exacerbation COPD patients with an AUC was 0.783(95%CI,0.666~0.900,P<0.001)and with the diagnostic accuracy was 69%. C-reactive protein in the acute exacer-bation of AUC diagnosis of COPD was 0.686(95%CI:0.549~0.823,P<0.01)and the diagnostic accuracy rate was 59%. Conclusion The plasma level of GDF-15 was significantly increased in COPD patients compared with people in the healthy control group. Plasma GDF-15 and C- reactive protein were highly correlated in the stable stage of COPD patients and in acute exacerbation stage of COPD patients. The diagnostic accuracy of GDF in patients with the stable stage of COPD and with acute exacerbation stage of COPD was higher than C-reactive pro tein.