To provide evidence for three-level prevention of cholelithiasis by means of observing the effects of some choleretics on bile compositions drained from patients with pigment gallstone. Methods: Twenty-seven patients...To provide evidence for three-level prevention of cholelithiasis by means of observing the effects of some choleretics on bile compositions drained from patients with pigment gallstone. Methods: Twenty-seven patients suffering from primary pigment gallstones and having received treatment of choledochostomies plus T-tube or endoscopic nasal bile drainage (ENBD) were divided equally into three groups, and administered respectively with Lidanling (利胆灵, the LDL group), ursodesoxycholic acid (the UDA group) and combination of LDL and UDA (the LDL+ UDA group) through oral intake(7 patients in each group). Besides, 6 post-operational patients got no treatment with any drug were allocated in the control group. Bile of all the patients was collected before treatment and on the 1, 3, 5, 7th day after the treatment started to detect levels of total bile acid (TBA), glycocholic acid (GCA), taurocholic acid (TCA), glycocholic cheno-desoxycholic acid (GCDCA), total bilirubin (TBIL), uncombined bilirubin ( UCB), concentration of calcium ion (Ca^2+ ) as well as the bacterio-genetic and endogenous 13-glucuronidase activity for comparing. Results: Levels of TBA, GCA, TCA and GCDCA got gradually increased in the UDA group and the LDL + UDA group after treatment ( P〈0. 05), while those in the LDL group remained unchanged, showing an insignificant difference as compared with those in the control group. In the LDL group and the LDL + UDA group, TBIL gradually increased while UCB gradually decreased in the course of treatment (P〈0. 05). Moreover, levels of Ca^2+ and endogenous β-glucuronidase activity got significantly lowered ( P〈0. 05). Conclusion: Combined use of LDL and UDA could elevate levels of TBA, GCA, TCA, GCDCA, enhance the excretion of TBIL in patients with pigment gallstone after bile drainage, lower levels of UCB and Ca^2+ and the activity of endogenous β-glucuronidase in the bile, so as to reduce the possibility of stone formation of bile, and therefore, it could be used to prevent the production of pigment gallstone, especially to prevent post-operative recurrence of stones.展开更多
Background:Although osteopontin(OPN)is expressed in the liver and pigment gallstones of patients with hepatolithiasis,its role in pigment gallstone formation remains unclear.This study aimed to explore the function of...Background:Although osteopontin(OPN)is expressed in the liver and pigment gallstones of patients with hepatolithiasis,its role in pigment gallstone formation remains unclear.This study aimed to explore the function of OPN in pigment gallstone formation.Methods:Rats were fed a chow diet(CD)or lithogenic diet(LD)for 10 consecutive weeks;blocking tests were then performed using an OPN antibody(OPN-Ab).Incidence of gallstones and levels of several bile components,OPN,tumor necrosis factor alpha(TNF-α),and cholesterol 7 alpha-hydroxylase(CYP7A1)were analyzed.To determine TNF-αexpression in hepatic macrophages and both CYP7A1 and bile acid(BA)expression in liver cells,recombinant rat OPN and recombinant rat TNF-αwere used to treat rat hepatic macrophages and rat liver cells,respectively.Chi-square or Fisher exact tests were used to analyze qualitative data,Student t-test or one-way analysis of variance were used to analyze qualitative data.Results:Incidence of gallstones was higher in LD-fed rats than in CD-fed rats(80%vs.10%,P<0.05).BA content significantly decreased in bile(t=-36.08,P<0.01)and liver tissue(t=-16.16,P<0.01)of LD-fed rats.Both hepatic OPN protein expression(t=9.78,P<0.01)and TNF-αlevel(t=8.83,P<0.01)distinctly increased in the LD group;what’s more,CYP7A1 mRNA and protein levels(t=-12.35,P<0.01)were markedly down-regulated in the LD group.Following OPN-Ab pretreatment,gallstone formation decreased(85%vs.25%,χ^(2)=14.55,P<0.01),liver TNF-αexpression(F=20.36,P<0.01)was down-regulated in the LD group,and CYP7A1 expression(F=17.51,P<0.01)was up-regulated.Through CD44 and integrin receptors,OPN promoted TNF-αproduction in macrophage(F=1041,P<0.01),which suppressed CYP7A1 expression(F=48.08,P<0.01)and reduced liver BA synthesis(F=119.4,P<0.01).Conclusions:We provide novel evidence of OPN involvement in pigmented gallstone pathogenesis in rats.展开更多
文摘To provide evidence for three-level prevention of cholelithiasis by means of observing the effects of some choleretics on bile compositions drained from patients with pigment gallstone. Methods: Twenty-seven patients suffering from primary pigment gallstones and having received treatment of choledochostomies plus T-tube or endoscopic nasal bile drainage (ENBD) were divided equally into three groups, and administered respectively with Lidanling (利胆灵, the LDL group), ursodesoxycholic acid (the UDA group) and combination of LDL and UDA (the LDL+ UDA group) through oral intake(7 patients in each group). Besides, 6 post-operational patients got no treatment with any drug were allocated in the control group. Bile of all the patients was collected before treatment and on the 1, 3, 5, 7th day after the treatment started to detect levels of total bile acid (TBA), glycocholic acid (GCA), taurocholic acid (TCA), glycocholic cheno-desoxycholic acid (GCDCA), total bilirubin (TBIL), uncombined bilirubin ( UCB), concentration of calcium ion (Ca^2+ ) as well as the bacterio-genetic and endogenous 13-glucuronidase activity for comparing. Results: Levels of TBA, GCA, TCA and GCDCA got gradually increased in the UDA group and the LDL + UDA group after treatment ( P〈0. 05), while those in the LDL group remained unchanged, showing an insignificant difference as compared with those in the control group. In the LDL group and the LDL + UDA group, TBIL gradually increased while UCB gradually decreased in the course of treatment (P〈0. 05). Moreover, levels of Ca^2+ and endogenous β-glucuronidase activity got significantly lowered ( P〈0. 05). Conclusion: Combined use of LDL and UDA could elevate levels of TBA, GCA, TCA, GCDCA, enhance the excretion of TBIL in patients with pigment gallstone after bile drainage, lower levels of UCB and Ca^2+ and the activity of endogenous β-glucuronidase in the bile, so as to reduce the possibility of stone formation of bile, and therefore, it could be used to prevent the production of pigment gallstone, especially to prevent post-operative recurrence of stones.
基金supported by a grant from the Beijing Municipal Natural Science Foundation(Number:7172233).
文摘Background:Although osteopontin(OPN)is expressed in the liver and pigment gallstones of patients with hepatolithiasis,its role in pigment gallstone formation remains unclear.This study aimed to explore the function of OPN in pigment gallstone formation.Methods:Rats were fed a chow diet(CD)or lithogenic diet(LD)for 10 consecutive weeks;blocking tests were then performed using an OPN antibody(OPN-Ab).Incidence of gallstones and levels of several bile components,OPN,tumor necrosis factor alpha(TNF-α),and cholesterol 7 alpha-hydroxylase(CYP7A1)were analyzed.To determine TNF-αexpression in hepatic macrophages and both CYP7A1 and bile acid(BA)expression in liver cells,recombinant rat OPN and recombinant rat TNF-αwere used to treat rat hepatic macrophages and rat liver cells,respectively.Chi-square or Fisher exact tests were used to analyze qualitative data,Student t-test or one-way analysis of variance were used to analyze qualitative data.Results:Incidence of gallstones was higher in LD-fed rats than in CD-fed rats(80%vs.10%,P<0.05).BA content significantly decreased in bile(t=-36.08,P<0.01)and liver tissue(t=-16.16,P<0.01)of LD-fed rats.Both hepatic OPN protein expression(t=9.78,P<0.01)and TNF-αlevel(t=8.83,P<0.01)distinctly increased in the LD group;what’s more,CYP7A1 mRNA and protein levels(t=-12.35,P<0.01)were markedly down-regulated in the LD group.Following OPN-Ab pretreatment,gallstone formation decreased(85%vs.25%,χ^(2)=14.55,P<0.01),liver TNF-αexpression(F=20.36,P<0.01)was down-regulated in the LD group,and CYP7A1 expression(F=17.51,P<0.01)was up-regulated.Through CD44 and integrin receptors,OPN promoted TNF-αproduction in macrophage(F=1041,P<0.01),which suppressed CYP7A1 expression(F=48.08,P<0.01)and reduced liver BA synthesis(F=119.4,P<0.01).Conclusions:We provide novel evidence of OPN involvement in pigmented gallstone pathogenesis in rats.