Rol de las polipíldoras en la reducción del riesgo cardiovascular en prevención primaria / Role of polypills in cardiovascular risk reduction in primary prevention

Resumen A diferencia de los medicamentos que contienen combinaciones de dosis fijas, como los recomendados por las guías clínicas para tratar la hipertensión arterial, las llamadas polipíldoras contienen varios fármacos que tratan simultáneamente dos o más afecciones cardiovasculares o factores de riesgo. Se propusieron hace 2 décadas, tanto para prevención primaria como secundaria, con la hipótesis de que tengan amplia difusión y penetración poblacional, es decir, que mejoren el uso de terapéuticas con probados beneficios en forma individual, gracias a un incremento en la adherencia de los pacientes al reducir el número de com primidos diarios y también al tener un costo igual o menor. En esta revisión simple, planteamos una mirada de la estratificación del riesgo distinta a la planteada por los puntajes clínicos y resumimos los beneficios de las polipíldoras en el tratamiento de los factores de riesgo y en la reducción de eventos cardiovasculares mayores. Adicionalmente, repasamos los mensajes clínicos del ensayo HOPE-3, que apuntan a controlar dos de las con diciones más prevalentes, como son la hipertensión arterial y el colesterol elevado, mediante una combinación de candesartán, hidroclorotiazida y rosuvastatina. Finalmente, proponemos su potencial indicación en un sistema sanitario heterogéneo como el de nuestro país, tanto a nivel poblacional basado en el riesgo intermedio o bajo, determinado intuitivamente o usando un calculador de riesgo, así como también en la atención personalizada que se practica en muchos escenarios sanitarios.

Abstract Unlike medications that contain fixed-dose combinations, such as those recommended by clinical guidelines for treating high blood pressure, the so-called polypills contain several drugs that simultaneously treat two or more cardiovascular conditions or risk factors. They were proposed 2 decades ago, both for primary and secondary prevention with the hypothesis that they could have wide dissemination and population penetration, improving the use of therapeutics with proven benefits individually, thanks to an increase in patient adherence by reducing the number of daily tablets and also by having an equal or lower cost. In this simple review, we present a look at risk stratification different from that posed by clinical scores and summarize the benefits of polypills in the treatment of risk factors and in the reduction of major cardiovascular events. Additionally, we review the clinical messages of the HOPE-3 trial, which aim to control two of the most prevalent conditions, such as high blood pressure and high cholesterol, through a combination of candesartan, hydrochlorothiazide and rosuvastatin. Finally, we propose its potential indication in a heterogeneous health system such as that of our country, both at the population level based on intermediate or low risk, determined intuitively or using a risk calculator, as well as in the personalized care that is practiced in many health scenarios.

The beneficial effects of virgin olive oil against oxidative stress induced by hypercholesterolemia in rats

Cardiovascular disease(CVD) remains the major cause of mortality in the world, typically claiming a third of all deaths. The primary cause of CVD is atherosclerosis. Therefore, timely prevention and therapy of atherosclerosis are able to reduce the risk of the development of its clinical manifestations. Anti-atherosclerotic activity of medicinal plants mainly appears in their multiple effects.This study was carried out to evaluate the hypolipidemic activity of virgin olive oil in experimentally induced hyperlipemic Wistar. A total of 24 rats were randomly allocated to 4 equal groups and treated as follows for 50 days: (1) Normal control (NC); that were fed with a standart diet; (2) High Cholesterol Diet Control (HCD); which received high cholesterol diet for 50 days; (3) Animals receiving high cholesterol diet for 50 days, after this period the animals are fed for eight days by the standard foodand receiving by gavage virgin olive oil (HCD+VOO) and(4) Animals fed for eight days with the standard food and receiving by gavage olive oil (VOO). High Cholesterol Diet containing yolk egg and coconut oil. Results showed that olive oil caused a significant (p < 0.01) reduction in serum levels of Total Cholesterol (TC), Triglycerides (TG), Low­Density Lipoprotein Cholesterol (LDL) and Atherogenic Index Serum (AIS). The results also demonstrated a significant (p < 0.01) increase in High­Density Lipoprotein Cholesterol (HDL). Moreover, virgin olive oil induced a significant reduction in liver lipid content. On the other hand, a High cholesterol diet induced oxidative stress was measured by estimating reduced glutathione level and amount of thiobarbituric acid reactive substances (TBARS) formed as an index of lipid peroxidation in a liver and a heart. Virgin olive oil supplementation attenuated all these variations. Our observations of the study indicate that the virgin olive oil has a significant antihyperlipidemic potential.

Evaluation of Anti-Hyperlipidaemic Activity of a Mixture of Zinger officinale, Allium sativum, Citrus Lemon, Honey, and Malus domestica Vinegar (ZACAH) Extracts in Rats Fed with High Cholesterol Diet

@#Introduction: The incidence and complications of hyperlipidemia associated co-morbidities and mortalities are grossly increasing globally. Intervention with natural products preparation has been identified as an alternative for the management of hyperlipidaemia and its related cardiovascular complications. This study investigated the anti-hyperlipidaemic activities of a mixture of Zinger officinale, Allium sativum, Citrus lemon, honey, and Malus domestica vinegar (ZACAH) extracts in in Sprague Dawley (SD) rats fed with high cholesterol diet. Methods: Thirty-six male SD rats were randomly distributed into 6 groups, including normal chow diet-fed (NC), high cholesterol diet (HCD), HCD+ Simvastatin (standard drug) while the remaining three groups were fed with HCD + ZACAH extracts at different doses (1, 3 and 5mg/kg body weight) for 18 weeks. Simvastatin at 10 mg/kg of bodyweight was used as control. High-performance liquid chromatography (HPLC) was used to determine phenolic compounds present in ZACAH extracts, elastase inhibitory assay was determined using spectrometric with a substrate (N-Succ-(Ala)3-pnitroanilide (SANA) while 2,2-diphenyl-1-picrylhydrazyl (DPPH) was performed based by the method described by Blois, 1958. Results: In vitro; ZACAH extracts had oxygen radical absorbance capacity (ORAC) value of 2000 µmol TE/100 mL, total phenolic content (TPC) of 7537 ± 54.5%, DPPH free radical scavenging activity of 27.34 ± 2.71%, elastase inhibitory assay of 29.29 ± 1.65% and lipoxygenase inhibitory assay of 98.58 ± 1.42%. In vivo, ZACAH extracts showed decreased bodyweight, adipose tissue, improved lipid profiles and hepatic biochemical enzymes. Conclusion: These results suggested that ZACAH extracts supplementation improved hyperlipidaemia in SD rats and might be a promising adjuvant for the treatment of hyperlipidaemia.

Effects of Peperomia pellucida (L.) methanolic extract on total cholesterol levels and liver histology of diet-induced hypercholesterolemic rats

Background@#Peperomia pellucida, locally known in the Philippines as pansit-pansitan, is an annual herb with many ethnomedicinal properties.@*Objective@#The study was conducted to evaluate the antihypercholesterolemic property of P. pellucida methanolic extract (PPME) through measurement of its effects on total blood cholesterol level and liver histology of hypercholesterolemic rats. @*Methodology@#Thirty experimental male rats were divided into six groups: Group I was fed with standard diet; Group II was fed with High Cholesterol Diet (HCD) only; Groups III, IV and V were fed with HCD and treated with PPME at 200, 400 and 800 mg kg-1 bwt respectively; Group VI was fed with HCD and treated with atorvastatin; and, Group 7 was fed with 400mg/kg PPME. Total Blood Cholesterol (TBC) levels were monitored, liver histology was analysed, and results were compared with the control and atorvastatin-treated group. @*Results@#Administration of different doses of PPME in hypercholesterolemic rats significantly reduced total blood cholesterol similar to Atorvastatin, a known anticholesterolemic drug. Furthermore, PPME particularly at a concentration of 400mg kg-1 bwt was effective in ameliorating liver damages induced by high cholesterol diet as shown by qualitative and quantitative histological assessment. @*Conclusion@#This investigation suggests that PPME at a concentration of 400 mg/kg bwt is a potential antihypercholesterolemic agent. Further studies have to be taken to better the understanding on the mechanisms of actions of PPME on how it modulates liver damage in hypercholesterolemic conditions.

The application of ultra-wide field fluorescein angiography in the evaluation of peripheral vascular changes following retinal vein occlusion / 中华实验眼科杂志

Objective To investigate the peripheral vascular findings in eyes with branch retinal vein occlusion (BRVO) and hemi-retinal vein occlusion (HRVO) using ultra-wide field fluorescein angiography (UWFFA),and analyze the influence of relative systemic factors on retinal vascular leakage.Methods A retrospective case-control study was designed.The 153 eyes of 146 patients with BRVO and 40 eyes of 40 patients with HRVO were include in Tianjin Medical University Eye Institute from September 2017 to March 2018.UWFFA was carried out in the patients,and the images were analyzed by Vantage Review software.The eyes were divided into two groups based on the whether the leakage occurred in other quadrant or fellow eye.The eyes with the fluorescence leakage only in the quadrant of affected vessel in late stage of UWFFA were in the RVO1 group,and the eyes with the fluorescence leakage in other quadrants or fellow eye besides affected vessel were in the RVO2 group.Relative past medical histories were recorded,such as hypertension,high cholesterol and diabetes mellitus.The influence of medical histories on vascular leakage in RVO1 group and RVO2 group with different histories was analyzed,respectively,and systemic factors which affected lcakage degree were evaluated.Results In 179 eyes with RVO,fluorescence leakage occurred in late stage of UWFFA besides affected vessel in 25 eyes (14.0％),including 19 eyes in the affected eyes (10.6％) and 6 eyes in fellow eyes (3.4％).Hypertension,high cholesterol and diabetes mellitus were found in 77,28 and 21 patients,respectively.In 77 hypertension patients,66 were in the RVO1 group,and 9 were in the RVO2 group (11.69％),and in 102 non-hypertension patients,86 were in the RVO1 group,and 16 were in the RVO2 group (15.69％),without significant difference was seen in the fluorescence leakage in other quadrants or fellow eye besides affected vessel between hypertension and non-hypertension patients (x2 =0.298,P =0.585).In 28 high cholesterol patients,24 were in the RVO1 group,and 4 were in the RVO2 group (14.29％),and in the 151 patients without high cholesterol,130 were in the RVO1 group,and 21 were in the RVO2 group (13.91％),without significant difference in the fluorescence leakage in other quadrants or fellow eye besides affected vessel between high cholesterol and non-high cholesterol (x2 =0.000,P =1.000).In 21 diabetes mellitus patients,17 patients were in the RVO1 group,and 4 patients were in the RVO2 group (19.05％),and in 158 patients without diabetes mellitus,137 were in the RVO1 group,and 21 were in the RVO2 group (13.29％),without significant difference was seen in the fluorescence leakage in other quadrants or fellow eye besides affected vessel between diabetes mellitus and non-diabetes mellitus (x2 =0.144,P=0.704).Conclusions Unexpected late peripheral retinal leakage can be seen on the UWFFA in the eyes with BRVO and HRVO.Hypertension,high cholesterol and diabetes mellitus are not the main cause of these findings.UWFFA can disclose more peripheral,wider retinal lesions.

Hypocholesterolemic effects of Kluyveromyces marxianus M3 isolated from Tibetan mushrooms on diet-induced hypercholesterolemia in rat

To investigate the effects of Kluyveromyces marxianus M3 isolated from Tibetan mushrooms on diet-induced hypercholesterolemia in rats, female Wistar rats were fed a high-cholesterol diet (HCD) for 28 d to generate hyperlipidemic models. Hyperlipidemic rats were assigned to four groups, which were individually treated with three different dosages of K. marxianus M3+HCD or physiological saline+HCD via oral gavage for 28 d. The total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels in the serum and liver of the rats were measured using commercially available enzyme kits. In addition, the liver morphology was also examined using hematoxylin and eosin staining and optical microscopy. According to our results, the serum and liver TC, TG, LDL-C levels and atherogenic index (AI) were significantly decreased in rats orally administered K. marxianus M3 (p <0.01), and the HDL-C levels and anti atherogenic index (AAI) were significantly increased (p <0.01) compared to the control group. Moreover, K. marxianus M3 treatment also reduced the build-up of lipid droplets in the liver and exhibited normal hepatocytes, suggesting a protective effect of K. marxianus M3 in hyperlipidemic rats.

Correlation between plasma nitric oxide and atherosclerotic lesion in rabbits / 西安交通大学学报(医学版)

ABSTRACT:Objective To analyze the correlation between plasma nitric oxide (NO)level and atherosclerotic lesion in high cholesterol-fed (HCD ) rabbits.Methods Twenty male Japanese white rabbits were divided randomly into two groups,which were fed with normal diet (control group,n =10)or HCD (experimental group, n =10 )for 1 6 weeks.At the end of the experiment,plasma lipid and NO levels were measured.The gross atherosclerotic lesions in each group were detected by Sudan IV staining while intimal lesion area was measured by hematoxylin/eosin (HE)and elastica van gieson (EVG).Moreover,the macrophages (MΦ)and smooth muscle cells (SMC)were detected by immunohistochemical staining.The correlation analysis was made to reveal the relationship between atherosclerotic lesions and plasma NO level.Results Compared with those in control group, the total cholesterol (TC),triglyceride (TG),low-density lipoprotein cholesterol (LDL-C)and NO levels all increased significantly in experimental group.Atherosclerotic lesions appeared on the vascular wall in the latter group.The area of atherosclerotic lesions and MΦ in the plaque had a positive association with plasma NO level. Conclusion There is a relationship between plasma NO level and the size of HCD-induced atherosclerotic lesions in rabbits.Meanwhile,the MΦ positive area in the atherosclerotic plaque is also associated with plasma NO level in cholesterol-fed rabbits,suggesting that plasma NO level may be associated with the occurrence and progress of early atherosclerosis.

Antidiabetic and antihyperlipidemic activity of hydroalcoholic extract of Withania coagulans Dunal dried fruit in experimental rat models.

Objective: Evaluation of antidiabetic potential of the hydroalcoholic extract of Withania coagulans Dunal dried fruit (WCDF) alone and in combination with glipizide, in streptozotocin‑induced diabetes, and evaluation of possible antihyperlipidemic activity of the same extract in high‑cholesterol diet‑induced hyperlipidemia, in albino rats. Materials and Methods: Experimental diabetes was induced in 30 albino rats with intraperitoneal injection of streptozotocin (55 mg/kg). The rats were divided into five groups receiving the following treatments orally for 4 weeks: Vehicle, glipizide (2.5 mg/kg), WCDF extract (1000 mg/kg), WCDF extract (1000 mg/kg) plus glipizide (1 mg/kg) and WCDF extract (1000 mg/kg) plus glipizide (2.5 mg/kg). Fasting and postprandial blood glucose levels were measured every week for 4 weeks. Endocrine pancreas histopathology was done at the end. In a separate set of experiment, five groups of six albino rats each, received orally for 4 weeks, vehicle, cholesterol (25 mg/kg/day), cholesterol (25 mg/kg/day) plus atorvastatin (7.2 mg/kg/day), cholesterol (25 mg/kg/day) plus WCDF extract (1000 mg/kg/day) and no treatment, respectively. Estimation of serum lipid profile and liver histopathology was done at the end of 4 weeks. Statistical Analysis: Between‑group and within‑group comparisons were respectively done by analysis of variance (ANOVA) and repeated measures ANOVA, followed by post hoc Tukey’s test, with a significance level of P < 0.05. Results and Conclusions: The 4‑week treatment with WCDF extract significantly reversed hyperglycemia in streptozotocin‑induced diabetes that was comparable to glipizide. When combined with glipizide (2.5 mg/kg), WCDF extract produced a synergistic antihyperglycemic effect as well as improvement in pancreatic histopathology. Moreover, hydroalcoholic extract of WCDF was effective and comparable to atorvastatin in controlling the high‑cholesterol diet‑induced hyperlipidemia in rats.

Effects of Water Extracts of Red Pepper Seeds Powder on Antioxidative Enzyme Activities and Oxidative Damage in Rats Fed High-Fat and High-Cholesterol Diets

The purpose of the present study was to examine the effects of water extracts from red pepper seeds powder on antioxidative enzyme activities and oxidative damage in groups of rrats fed high-fat and high-cholesterol diets group (HFC). The Rrats were divided into the following five experimental groups which are : composed ofa normal diet group, a high fat.high cholesterol diet group, and a high fat.high cholesterol diet group supplemented with different amounts contents (1%, 2% and 4%) of red pepper seeds powder water extracts supplemented groups (HFCW1, HFCW2 and HFCW4, respectively). Body weight gains and food intake were lower ofin the red pepper seed water extracts groups were lower than those inof the HFC group. Hepartic xanthine oxidase (XOD) activity was decreased in the HFCW2 and HFCW4 groups compared to the HFC group. Hepartic glutathione peroxidase (GSH-px) activitiyactivity was increased in the HFCW4 group compared to the HFC group. Hepatic superoxide radicals within the mitochondria and microsomes of cells were significantly reduced in the HFCW2 and HFCW4 groups compared to the HFC group. Hepartic hydrogen peroxide in the cytosol was significantly reduced in the HFCW3 and HFCW4 groups compared to the HFC group. Hepatic carbonyl values in the microsomes and mitochondria were significantly reduced in the HFCW4 group compared to the HFC group. Hepartic thiobarbituric acid reaction substance (TBARS) activity was decreased in the HFCW2 group compared to the HFC group. These results suggest that water extracts of red pepper seeds powder may reduce oxidative damage by activation of antioxidative defense systems in rats fed high fat.high cholesterol diets.

The effects of repeatedly heated frying oil and high cholesterol diet on the bone in ovariectomised rats

The use of repeatedly heated frying oils and intake of high cholesterol diet have been linked to bone damage. The aim of this study is to determine the combined effects of taking repeatedly heated frying oils (palm or soy oil) and high cholesterol diet on the dynamic histomorphometric parameters of bone. Ovariectomised rats were used as animal model of post-menopausal osteoporosis. After six months of treatment, Double-labeled Surface (dLS/BS), Mineralising surface (MS/BS) and Bone Formation Rate (BFR/BS) of ovariectomised rats (OvxC) were significantly reduced compared to the normal control group. Additions of fresh or once-heated palm or soy oil into high cholesterol diet seem to have improved the dynamic parameters towards the normal control values. However, when these oils were repeatedly heated, the protective effects were lost and the dynamic parameters except MS/BS dropped back towards the ovariectomised-control values.

Effects of Pioglitazone on Cytokine TNF-? of Adipocytes in High-cholesterol Model Rats / 中国药房

OBJECTIVE:To explore the effects of pioglitazone on secreation and mRNA expressions of TNF-? in adipocytes of high-cholesterol model rats.METHODS:30 rats fed with high-cholesterol diet for 8 weeks were randomly assigned to receive high cholesterol diet alone(high-cholesterol group,n=15) or high-cholesterol diet plus pioglitazone(3 mg?kg-1?d-1) (pioglitazone group,n=15) for 4 weeks.Another 15 rats were assigned to control group and fed with common diet for 12 weeks.Then the rats were sacrificed,with indexes such as blood lipid,serum concentration and mRNA expression of TNF-? in adipocytes of high-cholesterol rats determined.Besides,normal adipocytes were taken and treated with lipopolysaccharide and different concentrations of pioglitazone (0.1,1.0,10.0 ?mol?L-1) followed by a determination of TNF-? level and mRNA expression level.RESULTS:Compared with high-cholesterol group,serum concentration and mRNA expression of TNF-? in pioglitazone group were significantly lowered,but pioglitazone treatment showed little impact on blood sugar level and blood lipid level.Pioglitazone(0.1,1.0,10.0 ?mol?L-1) dose-dependently inhibited lipopolysaccharide-induced TNF-? secretion and mRNA expression in cultured adipocytes.CONCLUSION:Pioglitazone can reduce TNF-? level of fatty tissue and serum in high-cholesterol model rats.

Effect of Seeds Extract of Paeonia Lactiflora on Antioxidative System and Lipid Peroxidation of Liver in Rats Fed High-Cholesterol Diet

This study was conducted to investigate the antioxidative effects of Paeonia lactiflora (PL) seeds on antioxidative defense system and lipid peroxidation of liver in rats fed high-cholesterol diet. Sprague-Dawley male rats weighing 100+/-10g were randomly assigned into five experimental groups fed 0.5% cholesterol ; HC group which was not supplemented PL seeds extract, 0.1% methanol extract diet group (MP1 group), 0.2% methanol extract diet group (MP2 group), 0.05% ether-souble fraction diet group (EP1 group) and 0.1 % ether-souble fraction diet group (EP2 group). Experimental diets were fed ad libitum to the rats for 3 weeks. The activity of hepatic superoxide dismutase (SOD) was not significantly different among all the high cholesterol diet groups. The hepatic glutathione peroxidase (GSHpx) activity in MP2 group was increased to 27% compared to HC group. The activity of hepatic catalase (CAT) was not significantly different among the all high cholesterol diet groups. The hepatic glutathione S-transferase (GST) activity in the EP1 and EP2 groups were increased to 12% and 13%, respectively, as compared to HC group. The levels of hepatic TBARS in the MP1, MP2, EP1 and EP2 groups were reduced by 18%, 21%, 20% and 23%, respectively, as compared with HC group. The contents of lipofuscin in liver was not significantly different among all the experimental groups. The results indicated that PL seeds extract may be reduced oxidative damage by activating antioxidative defense system of hepatic in rats fed high-cholesterol diets.

Effect of Forsythia Viridissima Extracts on Antioxidative System and Lipid Peroxidation of Liver in Rats Fed High-Cholesterol Diet

This study was conducted to investigate the effects of Forsythia viridissima Lindl. (FVL) on antioxidative defense system and lipid peroxidation of liver in rats fed high-cholesterol diet. Sprague-Dawley male rats weighing 100+/-10 g were randomly assigned into five experimental groups fed 0.5% cholesterol ; HC group which was not supplemented FVL extract, 0.05% methanol extract diet group (MSI group), 0.1% methanol extract diet group (MS2 group), 0.025% ethylacetate-souble fraction diet group (ES1 group) and 0.05% ethylacetate-souble fraction diet group (ES2 group). Experimental diets were fed ad libitum to the rats for 3 weeks. The hepatic xanthine oxidase (XOD) activity in the MS2 group was decreased to 20% as compared to HC group. The activities of hepatic superoxide dismutase (SOD) and catalase (CAT) were not significantly different among all the high cholesterol diet groups. The hepatic glutathione peroxidase (GSHpx) activity in MS2, ES2 groups were significantly increased as compared to HC group. The hepatic glutathione S-transferase (GST) activity in the MS2 group was increased to 20% as compared to HC group. The levels of hepatic TBARS in the MS1, MS2, ES1 and ES2 groups were reduced by 13%, 21%, 13% and 21%, respectively, as compared with HC group. The contents of lipofuscin in liver tissue was not significantly different among all the experimental groups. The results indicate that FVL extract may reduce oxidative damage by activating antioxidative defense system of liver in rats fed high-cholesterol diets.

Electron Misoscopic Morphology of the Gallbladder and Gallstone Formation induced by High Cholesterol-Cholic Acid Diet in Mice / 대한간학회지

BACKGROUND/AIMS: The experimental production of cholesterol gallstone suggests that alteration of the nature of gallbladder mucus may be a factor in the induction of gallbladder stones. This study was designed to clarify the changes of the gallbladder epithelia and the role of a high cholesterol-cholic acid diet (CCD) in the formation of the gallstones. METHOD: Forty mice were fed on a diet of natural 1% high-cholesterol egg yolk and 2.5% cholic acid for 8 weeks. The mice were sacrificed biweekly and followed up for 8 weeks. The gallbladder tissues and bile were prepared for electron microscopic examination. We observed the ultrastructural changes of the epithelia and the sediments of the gallbladder bile with scanning and transmission electron microscopic observation. RESULTS: 1) Process of Gallstone formation in bile: At the 2nd week in mice fed with CCD, the crystals grew up by appositional layering into monoliths and then by aggregation into mulberry-shaped stones. At the 8th week many stones and numerous concrements were observed. 2) Scanning electron microscopic findings: In mice fed with CCD, the scattered whitish patches of epithelial cell surfaces exhibited the cauliflower-like apical protrusion secreting mucin. These protrusions appeared to be swellings of the apical plasmalemma and they were mixed with the mucus and microvilli. 3) Transmission electron microscope findings: At the 2nd week, numerous electron lucent secretory granules were observed in the apical zone of the epithelial cells. Increased numbers of fat vacuoles were also observed in the basal area of epithelium. Two types of cells were observed in the lining epithelium: dark and light cells. CONCLUSION: This study suggests that long-term administration of CCD, and the resultant increased secretion of glycoprotein from gallbladder epithelial cells, could be a factor in the induction of the gallstones.

Effect of activated macrophages on glycoprotein secretion from gallbladder tissue of guinea pig / 中华肝胆外科杂志

Objective To study the effects of high cholesterol diet and activated macrophages (M) on glycoprotein secretion from the gallbladder tissue of guniea pig.Method Forty guniea pigs were randomized into group A fed with ordinary diet and group B fed with a diet containing 1.2% cholesterol for one week.Glycoprotein secretion from guinea pig gallbladder was observed in tissue culture using ~3H-glucesamine as a precursor,and in the meantime,with hydrocortisone and activated M to understand the effects on glycoprotein synthesis and secre- tion function of gallbladder epithelium.Results The activity of peritoneal M was significantly increased in guinea pigs fed with high cholesterol diet.High cholesterol diet induced significant release of ~3H-glucosamine-labeled gly- coprotein into the tissue culture medium as compared with the control level of guinea pig fed with normal diet.The gallbladder tissues were co-cultured for 16 hours with peritoneal M of guinea pig fed with high cholesterol diet. Mucin secretion had an evident increase compared with the controls (with the peritoneal M of guinea pig fed with normal diet at 10~4,10~6 cell/ml).Hydrocortisone (10~(-6),10~(-5),10~(-4)mol/l) caused a reversible dose-dependent inhibition on glycoprotein secretion from the gallbadder tissues of guinea pig fed with high cholesterol diet.Hydro- cortisone (10~(-4)mol/l) also inhibited the stimulatory effect of M activated by high cholesterol diet on glycoprotein hypersecretion in the gallbladder tissues of guinea pig fed with ordinary diet.Conclusion (1) High cholesterol diet can induce the increase of glycoprotein secretion from gallbladder tissues of guinea pig;(2) M can be actvi- ated by high cholesterol diet,which stimulates glycoprotein secretion from the gallbladder tissues of guinea pig. Considering the results of experiment using an animal gallbladder stone model,these findings suggest that the hy- persecretion of glycuprotein from guinea pig gallbladder tissue may be related to guinea pig M activated by high cholesterol diet and stimulated to release TNF,IL-I,etc.