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1.
The purpose of the present study was to characterize possible effects of dietary-induced plasma lipid elevations on the development of arterial lesions in spontaneously hypertensive rats (SHR) and to reveal any influence of treatment with metoprolol on these parameters. Metoprolol treatment caused an 8% decrease in heart rate and a 13% decrease in blood pressure and led to a rise in plasma triglycerides, 24%, 17% and 34% after 1, 3 and 6 months of metoprolol treatment, respectively. However, no effect on plasma triglycerides was observed after 9 months of metoprolol treatment while a reduced cholesterolemic response was observed. Intimal proliferations containing accumulations of lipids were observed in small intramural branches of coronary arteries (greater than 100 microns) in 11 of 31 control rats fed the atherogenic diet for 9 months. In contrast, similar changes were observed in only 1 of 34 metoprolol-treated rats fed an otherwise identical diet. The corresponding figures for the frequency of lipid containing intimal plaques in aorta were 6/19 in controls and 2/24 in the metoprolol-treated group.  相似文献   

2.
Intimal lipid concentrations were determined in aortic biopsies obtained during coronary by-pass surgery. In addition serum lipoprotein and apolipoprotein levels were quantitated and their relationships to aortic intimal lipid concentrations were analysed. The possibility to use aortic intimal lipid and serum lipoprotein or apolipoprotein concentrations to predict clinical prognosis following the coronary by-pass operation was also evaluated. Intimal cholesterol, cholesterol ester, phosphatidylcholine and sphingomyelin were intercorrelated, whereas none of these lipid fractions correlated to aortic intimal triglyceride levels. Patients with hypertension had higher aortic intimal cholesterol ester levels than normotensive patients. There was a positive correlation between the number of stenosed coronary arteries and serum apo B or triglyceride levels. In addition there was a negative correlation between the number of stenosed arteries and HDL-cholesterol. Prognosis after the operation was inversely correlated to serum apo A-I levels. Our data do not, however, support the notion that aortic intimal lipid levels can be used to evaluate prognosis after coronary by-pass surgery.  相似文献   

3.
In order to investigate whether initial plasma lipid concentrations could be used to distinguish between high and low responders to an atherogenic diet, rabbits were divided into 3 groups according to their plasma concentrations of cholesterol and phospholipids after 4 weeks on a standard rabbit diet. Plasma cholesterol and phospholipid levels were less than 0.5 mM, less than 1.1 mM, respectively, in group 1 (n = 17), greater than 0.5 mM, less than 1.1 mM, in group 2 (n = 13), and greater than 0.5 mM, greater than or equal to 1.1 mM, in group 3 (n = 14). After 7 weeks on a diet containing 0.25% cholesterol and 3% coconut oil, animals in groups 1 and 2 had a lower increase in their plasma lipid levels compared with group 3. Half of each group was then treated with the beta 1-adrenoceptor antagonist metoprolol during the next 14 weeks on the atherogenic diet. At the end of the study, the extent of atherosclerosis both in the aortas and in the coronary arteries of the control animals showed a positive correlation to plasma cholesterol and to plasma phospholipid concentrations integrated over time. The metoprolol-treated animals in groups 1 and 2 had a reduction of atherosclerosis compared with their respective controls. We conclude that subpopulations of rabbits that react differently on an atherogenic diet can be identified by their initial plasma lipid levels, and that metoprolol treatment of low responders to an atherogenic diet significantly reduces atherosclerotic lesions of the aorta.  相似文献   

4.
Even when administered at a comparatively low level, dietary cholesterol produces significant changes in the properties of plasma lipoproteins in rats, particularly the d less than or equal to 1.006 g/ml fraction (VLDL). The occurrence of these changes is promoted by dietary casein. To test the hypothesis that these dietary-induced perturbations might include properties influencing lipoprotein-cell interactions of relevance to atherogenesis, cultured mouse peritoneal macrophages were incubated with VLDL isolated from male rats fed on diets containing either 0, 0.25 or 0.5% cholesterol with casein or soybean protein, respectively, as the sole source of protein. No increase in cholesteryl ester content, and a comparatively small rise in triglyceride content, was observed in macrophages incubated with VLDL from rats fed on cholesterol-free diets. In contrast, a significant and apparently saturable cellular accumulation of cholesteryl esters as well as triglycerides was produced by VLDL from cholesterol-fed rats. The curves showing cellular lipid accumulation versus VLDL-protein (or VLDL-cholesterol) content in the cell medium indicated different cellular affinity for VLDL from casein-fed rats in comparison with VLDL from soybean protein-fed rats. The apoprotein composition of VLDL differed between groups of rats fed on different types of dietary protein with higher proportions of apo C's in the casein-fed rats. In addition, cholesterol feeding resulted in increased proportions of apo A-I and apo A-IV in the plasma VLDL fraction.  相似文献   

5.
L Jacobsson 《Artery》1989,16(2):105-117
The susceptibilities of male and female mini-pigs of the G?ttingen strain to experimental hyperlipoproteinemia and atherosclerosis were studied and compared. Hyperlipoproteinemia was induced in groups of pigs of each sex by adding 11.2% egg yolk and 0.5% cholesterol to the diet. The initial increase in the plasma cholesterol concentration was significantly greater in the female animals than in the male ones. In both sexes most of the increase in plasma cholesterol was referable to the low-density lipoprotein fraction. As the experiment proceeded, the difference in the plasma cholesterol level between the sexes became less pronounced. After 18 months on the lipid-rich diet the animals were slaughtered and examined for atherosclerotic lesions. Specimens from the coronary arteries and the thoracic and abdominal aorta were taken for lipid analyses. From colour photographs of the intimal surface of the aorta, the percentage area of visible atherosclerosis in the abdominal part was calculated. Atherosclerotic lesions were present in the coronary arteries and in the abdominal aorta in both sexes. In the abdominal aorta, the results of the lipid analyses, and the calculated percentage area of atherosclerosis, indicated that the degree of atherosclerosis was similar in male and female pigs. In the coronary arteries, the atherosclerosis was more pronounced in the female pigs, as judged from the accumulation of cholesterol.  相似文献   

6.
The Triton WR-1339 technique was used in order to study age-dependent changes of the rate of very low-density lipoprotein (VLDL) lipid secretion in rats consuming either casein or soy protein isolate. There was a significantly higher influx of lipoprotein cholesterol and triglycerides into the plasma compartment (of fasted animals) after a casein than after a soy diet, both in 10-week-old animals (cholesterol: 0.78 +/- 0.06 vs. 0.52 +/- 0.03 mmol X 1(-1) X h-1) and 25-week-old animals (cholesterol: 0.50 +/- 0.07 vs. 0.32 +/- 0.05 mmol X 1(-1) X h-1), but secretion rates diminished with age. The higher secretion rates following casein were paralleled by higher serum cholesterol levels in the fasted younger animals and also, though to a lesser degree, in the fed animals. These data contribute further evidence to our earlier proposal that dietary protein may induce different serum lipid levels by the modulating rate of lipid influx into the plasma compartment.  相似文献   

7.
Male Mongolian gerbils (Meriones unguiculatus) were fed casein or soy protein in the presence and absence of dietary cholesterol for 15 months. Diets resembled the average North American diet in energy contributions from protein, fat and carbohydrate, cholesterol content and fatty acid profile. At month 0, 3, 6, 9, 12 and 15, plasma samples were analyzed for total cholesterol (TC), HDL cholesterol (HDLC) and triglyceride (TG) concentrations. Plasma LDL cholesterol (LDLC) was estimated indirectly. Liver TC was also determined at these time points. Comparisons of protein source and cholesterol level were averaged over the 15 month period. Casein-fed gerbils had significantly higher plasma TC and TG levels and lower HDLC levels (as a percent of TC) compared to soy-fed animals, independent of the presence or absence of dietary cholesterol. LDLC was significantly elevated in casein-fed gerbils only when cholesterol was present in the diet. Elevations in plasma TC levels were reflected by elevations in liver TC. Despite plasma lipid elevations that are consistent with the development of atherosclerosis (AS) and coronary heart disease (CHD) in humans, hyperlipidemic gerbils do not develop AS. Further characterization of gerbil lipid metabolism responses to dietary alterations aimed at the prevention of CHD in humans is necessary to elucidate the mechanism for the gerbil's resistance to AS.  相似文献   

8.
The sera of coronary patients with angiographically-documented stenosis of 1 to 3 coronary arteries caused a two-to-fivefold accumulation of intracellular cholesterol in intact human aortic intimal cell culture. This property, qualified as "atherogenic", was exhibited by the sera of 90% of the coronary patients examined (97 males and females, aged 29 to 55 years). Only 20% of normal subjects revealed atherogenic properties in cell cultures. The capacity of the sera to accumulate intracellular cholesterol was unrelated to the levels of total cholesterol, high density lipoprotein cholesterol, apo-B or apo-AI, taken separately, but showed a weak correlation to the apo-B/apo-AI ratio. The sera of coronary patients caused lipid accumulation in human aortic medial smooth-muscle cells and blood mononuclear cells, in human and mouse peritoneal macrophages, but never in human aortic or umbilical vein endothelial cells, nor human embryo fibroblasts.  相似文献   

9.
Hyperlipidemia may increase endothelial damage and promote accelerated atherogenesis in graft coronary vasculopathy. To study the effects of hypercholesterolemia on coronary endothelial dysfunction, intimal hyperplasia, and lipid content, a porcine model of heterotopic heart transplantation, allowing nonacute rejection without immunosuppressive drugs, was used. A high cholesterol diet was fed to donor and recipient swine 1 month before and after transplantation. The endothelial function of coronary arteries of native and transplanted hearts from cholesterol-fed animals was studied in organ chambers 30 days after implantation and compared with endothelial function in arteries from animals fed a normal diet. The total serum cholesterol increased 3-fold in donors and recipients. Endothelium-dependent relaxations to serotonin, to the alpha(2)-adrenergic agonist UK14,304, and to the direct G-protein activator sodium fluoride were decreased significantly in allografted hearts compared with native hearts from both groups. Relaxations to the calcium ionophore A23187 and bradykinin were decreased significantly in allografts from animals fed the high cholesterol diet. The prevalence of intimal hyperplasia was significantly increased in coronary arteries from hypercholesterolemic swine. There was a significant increase in the lipid content of allograft arteries of hypercholesterolemic recipients. Hypercholesterolemia causes a general coronary endothelial dysfunction, increases the prevalence of intimal hyperplasia, and augments the incorporation of lipids in the vascular wall after heart transplantation. Hyperlipidemia accelerates graft coronary atherosclerosis through its effects on the endothelium.  相似文献   

10.
目的探讨卡维地洛与美托洛尔对2型糖尿病合并冠心病病人糖、脂代谢影响。方法确诊为2型糖尿病合并冠心病病人116例,随机分成2组,分别接受卡维地洛和美托洛尔治疗,随访6个月,检查治疗前后血糖、血脂及其相关指标变化。结果卡维地洛治疗组空腹血糖及胰岛素水平、血脂水平均比治疗前有下降,而美托洛尔治疗组血糖水平较前升高,血脂水平改变不明显。结论卡维地洛与美托洛尔治疗糖尿病合并冠心病病人对糖、脂代谢的影响差异有统计学意义。  相似文献   

11.
Rats fed a high-cholesterol semipurified diet containing casein developed higher levels of serum cholesterol than soy-fed animals. The hypercholesterolaemia of casein-fed rats was due to accumulation of very low density lipoproteins (VLDL), as measured by increased concentrations of serum VLDL cholesterol, protein and apoprotein B. High density lipoprotein (HDL) cholesterol was similar for the two dietary groups. Cholesterol absorption, as measured by the dual isotope ratio method and by direct measurement of cholesterol secretion into thoracic duct lymph, did not differ between the two groups. Cholesterol kinetics were derived from plasma cholesterol specific radioactivity curves and the casein-fed rats had a similar rate of plasma cholesterol production, but a significantly lower plasma cholesterol fractional catabolic rate (FCR) compared with the soy-fed rats. Kinetics of plasma VLDL apoprotein B, derived from analysis of reinjected 125I-labelled VLDL protein, also showed a lower fractional catabolic rate with casein feeding. This suggests that the accumulation of VLDL in the plasma of rats fed dietary casein is not due to excess VLDL production but to deficient VLDL removal. The hypercholesterolaemia appears to be a consequence of diminished VLDL catabolism.  相似文献   

12.
Pantethine (P), a coenzyme A precursor, was administered to cholesterol-fed rabbits (0.5% cholesterol diet + 1% pantethine) for 90 days. At the end of treatment, plasma total cholesterol levels were reduced 64.7% and the HDL/total cholesterol ratio increased in P-treated animals; a significant rise of the apo A-I/A-II ratio was detected in HDL. VLDL lipid and protein levels were, on the other hand, reduced by P. The cholesterol-ester content of both liver and aortic tissues was not significantly affected by P. Although the total aortic area with evident plaques was reduced only 18.2%, the microscopical examination of sections from the major vessels of P-treated animals, showed a reduction in the severity of lesions, both in the aorta and in the coronary arteries. These findings suggest that P, in addition to significantly lowering plasma cholesterol levels in rabbits on an experimental diet, may modify lipid deposition in major arteries, possibly by affecting lipoprotein composition and/or exerting an arterial protective effect.  相似文献   

13.
The effects of long-term high-fiber diet on lipid and glucose levels and the histological changes in the coronary arteries and thoracic aorta in STZ-induced diabetic SD rats were investigated. During the first 4 weeks of the study period, all diabetic rats were given regular chow plus water after which, all were grouped according to the following diet regimen: group II, no added cholesterol and glucomannan; group III, no added cholesterol but with glucomannan supplement, group IV, with added cholesterol but no glucomannan supplement; and group V, with both cholesterol and glucomannan supplements. 15% weight of glucomannan and 1.5% weight of cholesterol in regular rat chow were used as supplements when indicated. Non-diabetic rats which received only regular chow served as the control group (group I). In the 18th week all rats were sacrificed and weight gain, glucose, total cholesterol, HDL-cholesterol, triglyceride and lipid peroxidase concentrations were determined. Selected portions of the heart and thoracic aorta were histologically examined. Weight gain was higher in rats supplemented with glucomannan than in those without glucomannan supplements, but the difference is not significant. A lowering tendency in glucose levels was likewise observed. Furthermore, total cholesterol and HDL-cholesterol levels were lower and higher, respectively in diabetic rats receiving glucomannan. Although the triglyceride levels were similar in all rats, lipid peroxidase levels were significantly lower in rats with high-fiber diet.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

14.
Many patients with hypertrophic cardiomyopathy have signs and symptoms of myocardial ischemia and dysfunction. Although hypertrophy and increased left ventricular pressure can account for such abnormalities, altered small intramural coronary arteries have also been described in such patients. To determine the prevalence and extent as well as the clinical relevance of abnormal intramural coronary arteries, a histologic analysis of left ventricular myocardium obtained at necropsy was performed in 48 patients with hypertrophic cardiomyopathy (but without atherosclerosis of the extramural coronary arteries) and in 68 control patients with either a normal heart or acquired heart disease. In hypertrophic cardiomyopathy, abnormal intramural coronary arteries were characterized by thickening of the vessel wall and a decrease in luminal size. The wall thickening was due to proliferation of medial or intimal components, or both, particularly smooth muscle cells and collagen. Of the 48 patients with hypertrophic cardiomyopathy, 40 (83%) had abnormalities of intramural coronary arteries located in the ventricular septum (33 patients), anterior left ventricular free wall (20 patients) or posterior free wall (9 patients); an average of 3.0 +/- 0.7 abnormal arteries were identified per tissue section. Altered intramural coronary arteries were also significantly more common in tissue sections having considerable myocardial fibrosis (31 [74%] of 42) than in those with no or mild fibrosis (31 [30%] of 102; p less than 0.001). Abnormal intramural coronary arteries were also identified in three of eight infants who died of hypertrophic cardiomyopathy before 1 year of age. In contrast, only rare altered intramural coronary arteries were identified in 6 (9%) of the 68 control patients (0.1 +/- 0.05 abnormal arteries per section; p less than 0.001) and those arteries showed only mild thickening of the wall and minimal luminal narrowing. Moreover, of those patients with abnormal intramural coronary arteries, such vessels were about 20 times more frequent in patients with hypertrophic cardiomyopathy (0.9 +/- 0.2/cm2 myocardium) than in control patients (0.04 +/- 0.02/cm2 myocardium). Hence, abnormal intramural coronary arteries with markedly thickened walls and narrowed lumens are present in increased numbers in most patients with hypertrophic cardiomyopathy studied at necropsy and may represent a congenital component of the underlying cardiomyopathic process.(ABSTRACT TRUNCATED AT 400 WORDS)  相似文献   

15.
Objectives. This study was designed to test the hypothesis that long-term oral supplementation of dietary l-arginine (to provide a sustained elevation of nitric oxide activity) would inhibit atherogenesis in hypercholesterolemic rabbits, as assessed by histomorphometric measurements.Background. Endothelium-derived nitric oxide inhibits a number of processes that are critical in atherogenesis. Hypercholesterolemia reduces endothelial nitric oxide activity, and we postulate that this may promote atherogenesis. This reduction in nitric oxide activity can be reversed acutely by intravenous infusion of l-arginine, the precursor of nitric oxide. We show that dietary supplementation of l-arginine abrogates the development of coronary atheroma in hypercholesterolemic rabbits.Methods. Male New Zealand White rabbits were fed normal rabbit chow, 1% cholesterol chow or 1% cholesterol chow with dietary arginine or methionine supplementation to increase their intake of these amino acids sixfold. After 1 or 10 weeks of dietary intervention, the left main and left anterior descending coronary arteries were harvested for histologic study. Plasma cholesterol measurements were elevated to the same degree in all groups of rabbits receiving the 1% cholesterol diet, whereas plasma arginine levels were doubled in the arginine-treated group. High density lipoprotein (HDL) cholesterol values were not affected by arginine treatment.Results. In rabbits receiving the 1% cholesterol diet, with or without methionine supplementation, light and electron microscopy revealed a marked increase from 1 to 10 weeks in the intimal accumulation of macrophages, associated with an increase in the intimal area of the left main coronary artery. By contrast, in arginine-treated hypercholesterolemic rabbits, there was a near absence of adherent monocytes and tissue macrophages and no progression of intimal thickness from 1 to 10 weeks.Conclusions. Dietary supplements of l-arginine prevent intimal thickening in the coronary arteries of hypercholesterolemic rabbits. This antiatherogenic effect is not due to an alteration in plasma total cholesterol, HDL cholesterol or caloric or nitrogen balance. The data are consistent with the hypothesis that nitric oxide has antiatherogenic properties.  相似文献   

16.
The aim of our study was to estimate the cholesterol concentrations in high density lipoprotein subfractions (HDL2 i HDL3) in plasma of patients with normocholesterolemia and atherosclerosis of coronary arteries and in patients with myeloproliferative diseases. Blood samples from patients with normal plasma cholesterol levels were analyzed in spite of the fact that atherosclerosis of coronary arteries usually exist with hypercholesterolemia and myeloproliferative diseases usually coexist with hypocholesterolemia. In this way we wanted to determine changes in HDL2 i HDL3 metabolism which occur independently from changes of cholesterol levels in other lipoproteins. Our results showed that in patients suffering from atherosclerosis of coronary arteries with normolipemia the lowering of plasma cholesterol level in subfractions HDL2 and HDL3 was observed. In patients with myeloproliferative disease with normocholesterolemia the slight lowering of cholesterol level in subfraction HDL3 may be connected with moderate hypertriglyceridemia. In both groups of patients the lowering of HDL cholesterol in plasma was accompanied with the increased lipid peroxidation.  相似文献   

17.
OBJECTIVES: We examined the relationship between coronary endothelium-dependent vasodilation in response to bradykinin (BK) and plasma levels of oxidized low-density lipoprotein (oxLDL) in subjects with normal coronary arteries. BACKGROUND: It is unclear whether the plasma oxLDL level is a determinant of coronary endothelial function. Bradykinin plays an important role in regulating resting coronary tone and flow-mediated coronary vasomotion. METHODS: Coronary blood flow (CBF) in the left anterior descending (LAD) coronary artery was assessed by quantitative angiography and a Doppler flow wire in 94 consecutive subjects with normal coronary arteries. The plasma oxLDL level was measured by enzyme-linked immunosorbent assay using DLH3R, a specific antibody against oxLDL. RESULTS: Plasma levels of oxLDL in diabetic subjects (n = 13) were higher than those in non-diabetic subjects (n = 81). Plasma levels of oxLDL correlated with body mass index (BMI). Bradykinin at doses of 0.2, 0.6, and 2.0 microg/min caused dose-dependent increases in diameter and CBF in the LAD coronary artery. By a univariate analysis, oxLDL levels significantly correlated with epicardial (r = -0.30, p < 0.0001) and resistant (r = -0.36, p = 0.003) coronary vasodilator responses to BK at 2.0 microg/min, whereas total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were not associated with these coronary responses. In a stepwise multivariate analysis, oxLDL levels were significantly correlated with epicardial and resistant coronary vasomotor responses to BK, independent of age, gender, smoking status, other lipid levels, BMI, hypertension, and diabetes. CONCLUSIONS: The plasma level of oxLDL is an appropriate surrogate for assessing coronary endothelial-dependent vasomotor function as estimated by responses to BK compared with conventional risk factors for atherosclerosis.  相似文献   

18.
Summary Lipid accumulation in muscular (pulmonary, coronary and tibial) arteries and elastic (aorta and pulmonary) arteries of streptozotocin diabetic (65 mg/kg) rats was studied with an electron microscope. Arterial tissue specimens taken 4 days after the induction of diabetes showed lipid deposits in smooth muscle cells in the muscular arteries of 9 out of 24 diabetic rats, but in none of the 17 control rats. Histochemically the lipid was identified as triacylglycerol. Lipid accumulation was not seen in the elastic arteries of either diabetic or control rats. The diabetic animals with lipid deposits had slightly but significantly higher plasma glucose concentrations (p<0.02), higher non-esterified fatty acids levels (p<0.01), and lower concentrations of plasma insulin (p<0.02) than those without arterial deposits. The amount of lipid deposited in the arteries was closely related to the plasma non-esterified fatty acid level, which was in the ranges 0.8–1.1 mmol/l in diabetic rats without deposits, and 1.1–2.4 mmol/l in those with deposits. The findings suggest that lipid accumulation in smooth muscle cells of muscular arteries during acute diabetes could result from the high plasma non-esterified fatty acid concentrations.  相似文献   

19.
Effects of soybean protein, casein and whole egg protein on various indices for lipid biosynthesis in the liver were compared in fasted-refed rats. Soybean protein compared to casein and whole egg protein significantly reduced activities of glucose 6-phosphate dehydrogenase and fatty acid synthetase. The protein source also slightly reduced the activity of the malic enzyme. Soybean protein compared to other proteins not only reduced the microsomal triacylglycerol but also phosphatidylcholine syntheses when the activities were measured with endogenous diacylglycerol substrate. The protein-dependent changes disappeared, if artificial dispersion of dioleoylglycerol was employed as a substrate. The concentrations of microsomal diacylglycerol and triacylglycerol in whole liver in rats fed soybean protein were lower than those fed other proteins. When the diets containing soybean protein and casein were supplemented with DL-methionine (0.5 and 0.3%, respectively) to meet the nutritional requirement of the animals, soybean protein-dependent reductions in these indices for lipid biosynthesis were still detectable but considerably attenuated. Thus, it is plausible that a soybean protein-dependent decrease in fatty acid synthesis reduced the availability of microsomal diacylglycerol substrate for triacylglycerol synthesis and in turn modified hepatic triacylglycerol concentration. The dietary availability of sulfur amino acids may, at least in part, be responsible for the consequence observed in the present study.  相似文献   

20.
The atherogenic and cholesterolemic effects of animal protein vis-a-vis plant protein are well documented. Virtually all the studies were carried out using diets high in saturated fat, such as coconut oil. In order to determine if the same effects were seen with less saturated fat, we have compared atherogenic effects of an animal protein (casein) with those of a plant protein (soybean protein isolate) fed with partially hydrogenated soybean oil (PHS) (iodine value 72) or soybean oil (iodine value 134) as part of a cholesterol-free semipurified diet. After 6 months only rabbits fed casein-PHS exhibited elevated levels of plasma and liver cholesterol and triglycerides and atherosclerosis. Rabbits fed soy protein-PHS had slightly higher plasma cholesterol and triglycerides than did those fed soy protein and soybean oil, but values in both groups were in the normal range. The different effects of animal and plant protein on lipidemia and atherosclerosis can be influenced by dietary fat and appear to be dependent on fat saturation.  相似文献   

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