Expression of ceramide-metabolising enzymes in subcutaneous and intra-abdominal human adipose tissue

ABSTRACT: BACKGROUND: Inflammation and increased ceramide concentrations characterise adipose tissue of obese women with high liver fat content compared to equally obese women with normal liver fat content. The present study characterises enzymes involved in ceramide metabolism in subcutaneous and intra-abdominal adipose tissue. METHODS: Pathways leading to increased ceramide concentrations in inflamed versus non-inflamed adipose tissue were investigated by quantifying expression levels of key enzymes involved in ceramide metabolism. Sphingomyelinases (sphingomyelin phosphodiesterases SMPD1-3) were investigated further using immunohistochemistry to establish their location within adipose tissue, and their mRNA expression levels were determined in subcutaneous and intra-abdominal adipose tissue from both non-obese and obese subject. RESULTS: Gene expression levels of sphingomyelinases, enzymes that hydrolyze sphingomyelin to ceramide, rather than enzymes involved in de novo ceramide synthesis, were higher in inflamed compared to non-inflamed adipose tissue of obese women (with high and normal liver fat contents respectively). Sphingomyelinases were localised to both macrophages and adipocytes, but also to blood vessels and to extracellular regions surrounding vessels within adipose tissue. Expression levels of SMPD3 mRNA correlated significantly with concentrations of different ceramides and sphingomyelins. In both non-obese and obese subjects SMPD3 mRNA levels were higher in the more inflamed intra-abdominal compared to the subcutaneous adipose tissue depot. CONCLUSIONS: Generation of ceramides within adipose tissue as a result of sphingomyelinase action may contribute to inflammation in human adipose tissue.     

Grape peel powder attenuates the inflammatory and oxidative response of experimental colitis in rats by modulating the NF-κB pathway and activity of antioxidant enzymes

Most phenolic compounds and dietary fiber reach intact to the colon. We hypothesized that grape peel powder (GPP), a rich source of these bioactive compounds, modulates inflammatory and oxidative pathways collaborating to attenuate colonic damage in experimental colitis. To determine which bioactive fraction would be responsible for this effect, the aim of this study was to evaluate the effect of dietary supplementation with whole GPP or the isolated bioactive-rich fractions from GPP (extractable polyphenols [EP], dietary fiber and fiber-bound polyphenols [NEP-F], and dietary fiber) in rats with experimental colitis. Colitis was induced by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS) after 15 days of dietary supplementation. EP diet did not reverse the decrease in feed intake and indeed worsened colon shortening and increased spleen weight; however, these effects were not observed for the GPP group, which had polyphenols associated to the matrix besides the extractable ones. Colitis impaired the activity of colonic antioxidant enzymes and increased lipid peroxidation, protein oxidation, nitric oxide (NO) levels, and proinflammatory cytokines in serum and in the colon tissue. GPP restored the activity of antioxidant enzymes and decreased colon oxidation and NO levels. All grape peel fractions reduced the protein expression of the inhibitor of kappa kinase beta and NO levels in colon tissue, but only NEP-F reduced the expression of phosphorylated nuclear factor kappa B and myeloperoxidase activity. Results demonstrated that GPP attenuates inflammatory and oxidative response in TNBS–induced colitis by downregulating the nuclear factor kappa B pathway and upregulating antioxidant enzymes, with NEP-F being the fraction most likely associated to these protective effects.     

Inflammatory response to particles in the rat lung: secretion of acid and neutral proteinases by bronchoalveolar leucocytes.

Leucocyte proteinases are considered to be central to the tissue damage that is associated with chronic inflammatory lung disease. Both acid and neutral proteinases have the ability to degrade connective tissue molecules and both may therefore play a part in tissue proteolysis in inflamed lungs. In this study we have used a rat model of lung inflammation to investigate levels of acid and neutral proteinase activity in the bronchoalveolar region of control and inflamed lungs. We assessed the ability of proteinases, secreted by resident and inflammatory bronchoalveolar leucocytes, to damage the connective tissue molecule fibronectin. Inflammatory bronchoalveolar leucocytes had greater ability to mediate connective tissue damage than had resident alveolar macrophages and the tissue proteolysis was mediated, in the main, by proteinases active at neutral rather than at acid pH. The increased secretion of proteinase by inflammatory leucocytes was dependent on in vivo stimulation: exposing resident or inflammatory bronchoalveolar leucocytes in vitro to particulate or soluble stimuli had no effect in increasing their ability to degrade fibronectin or secrete the inflammogenic proteinase, plasminogen activator. Thus, neutrophils in the bronchoalveolar region of the rat lung have proteolytic activity which is mediated largely by neutral proteinases.     

Effect of carbohydrate overfeeding on whole body and adipose tissue metabolism in humans

OBJECTIVE: To evaluate the effect of a 4-day carbohydrate overfeeding on whole body net de novo lipogenesis and on markers of de novo lipogenesis in subcutaneous adipose tissue of healthy lean humans. RESEARCH METHODS AND PROCEDURES: Nine healthy lean volunteers (five men and four women) were studied after 4 days of either isocaloric feeding or carbohydrate overfeeding. On each occasion, they underwent a metabolic study during which their energy expenditure and net substrate oxidation rates (indirect calorimetry), and the fractional activity of the pentose-phosphate pathway in subcutaneous adipose tissue (subcutaneous microdialysis with 1,6(13)C2,6,6(2)H2 glucose) were assessed before and after administration of glucose. Adipose tissue biopsies were obtained at the end of the experiments to monitor mRNAs of key lipogenic enzymes. RESULTS: Carbohydrate overfeeding increased basal and postglucose energy expenditure and net carbohydrate oxidation. Whole body net de novo lipogenesis after glucose loading was markedly increased at the expense of glycogen synthesis. Carbohydrate overfeeding also increased mRNA levels for the key lipogenic enzymes sterol regulatory element-binding protein-1c, acetyl-CoA carboxylase, and fatty acid synthase. The fractional activity of adipose tissue pentose-phosphate pathway was 17% to 22% and was not altered by carbohydrate overfeeding. DISCUSSION: Carbohydrate overfeeding markedly increased net de novo lipogenesis at the expense of glycogen synthesis. An increase in mRNAs coding for key lipogenic enzymes suggests that de novo lipogenesis occurred, at least in part, in adipose tissue. The pentose-phosphate pathway is active in adipose tissue of healthy humans, consistent with an active role of this tissue in de novo lipogenesis.     

Studies on the effect of monosodium glutamate [MSG] administration on some antioxidant enzymes in the arterial tissue of adult male mice

The subcutaneous administration of monosodium glutamate to normal adult male mice at dose levels of 4 and 8 mg/g body weight caused a significant increase in lipid peroxidation level in the arterial tissue. The levels of total sulfhydryl and protein-bound sulfhydryl groups were found to be significantly increased, whereas non-protein-bound sulfhydryl, representing the glutathione level, was significantly decreased. It was also observed that the administration of monosodium glutamate at a dose level of 4 mg/g body weight and above induced oxidative stress by significantly lowering the activities of antioxidant enzymes like superoxide dismutases, catalase, and glutathione metabolizing enzymes like glutathione reductase and glutathione peroxidase in the arterial tissue.     

A reduced protein diet induces stearoyl-CoA desaturase protein expression in pig muscle but not in subcutaneous adipose tissue: relationship with intramuscular lipid formation

A reduced protein diet (RPD) is known to increase the level of intramuscular lipid in pig meat with a smaller effect on the amount of subcutaneous adipose tissue. This might be due to tissue-specific activation of the expression of lipogenic enzymes by the RPD. The present study investigated the effect of a RPD, containing palm kernel oil, soyabean oil or palm oil on the activity and expression of one of the major lipogenic enzymes, stearoyl-CoA desaturase (SCD) and on the level of total lipids and the fatty acid composition of muscle and subcutaneous adipose tissue in pigs. The RPD significantly increased SCD protein expression and activity in muscle but not in subcutaneous adipose tissue. The level of MUFA and total fatty acids in muscle was also elevated when the RPD was fed, with only small changes in subcutaneous adipose tissue. A positive significant correlation between SCD protein expression and total fatty acids in muscle was found. The results suggest that an increase in intramuscular but not subcutaneous adipose tissue fatty acids under the influence of a RPD is related to tissue-specific activation of SCD expression. It is suggested that the SCD isoform spectra in pig subcutaneous adipose tissue and muscle might be different.     

Prophylactic parenteral cefuroxime: subcutaneous concentrations in laparotomy wounds

Plasma and subcutaneous adipose tissue cefuroxime concentrations were measured in laparotomy wounds, by means of high-pressure liquid chromatography, in 12 patients undergoing elective abdominal operations. After intravenous administration of 1.5 g cefuroxime at induction of anaesthesia, the measured concentrations in serum and wound tissue during a 2 h period were above the MIC 90 of most micro-organisms derived from the alimentary tract. Tissue peak levels were reached within 15 min and the tissue half life was 1.5 h.     

葛根素联合雌二醇对去卵巢大鼠骨组织及血钙、磷和碱性磷酸酶的影响

目的:了解小剂量葛根素联合雌二醇对去卵巢大鼠的骨组织、血钙、磷和碱性磷酸酶的影响,为中西医结合治疗绝经后骨质疏松症提供实验依据。方法:5月龄健康雌性大白鼠120只,分成5个实验组(每组24只):①假手术组(sham);②去卵巢模型组(OVX);③葛根素组(Pr),皮下注射葛根素,50 mg/kg,1次/d;④雌二醇组(E2),皮下注射雌二醇200μg/kg,2次/周;⑤小剂量葛根素+雌二醇组(Pr+E2),皮下注射雌二醇100μg/kg,2次/周和葛根素25 mg/kg,1次/d。各实验组在第4、8、12和20周,随机取6只大鼠取股骨切片观察骨组织,采血测量血钙、磷和碱性磷酸酶,数据进行统计学分析。结果:OVX组第4、8、12、20周的骨组织呈骨质疏松病理改变,血钙、磷明显低于sham组(P﹤0.01),OVX组的第4、8、12、20周血碱性磷酸酶均明显高于sham组(P﹤0.01)。3个治疗组各时间的骨组织和血钙、磷和碱性磷酸酶与sham组无统计学意义(P﹥0.05)。小剂量的葛根素联合雌二醇治疗能使去卵巢大鼠骨组织和血钙、磷和血碱性磷酸酶基本恢复正常(P﹥0.05),与较大剂量的葛根素组或较大剂量的雌二醇组相比无统计学意义(P﹥0.05)。结论:小剂量的雌二醇与葛根素对去卵巢大鼠的骨质疏松症的治疗效果与单独使用较大剂量的葛根素或较大剂量的雌二醇相比治疗效果相近。     

经皮椎体成形术治疗脊柱压缩性骨折的效果及对患者炎性因子水平影响

目的 探讨经皮椎体成形术治疗脊柱压缩性骨折的效果及对患者炎性因子水平的影响。方法 70例脊柱压缩性骨折患者随机分为两组各35例,对照组采用椎体后凸成形术治疗,观察组采用经皮椎体成形术治疗,比较两组的手术指标、疼痛程度及炎性因子水平。结果 观察组的手术时间短于对照组,术中出血量与骨水泥注入量均低于对照组,术后伤椎增加高度高于对照组,术后1 d、 3 d、 7 d的VAS评分均低于对照组,术后CRP、 PCT及IL-6水平均低于对照组（P <0.05）。结论 经皮椎体成形术治疗脊柱压缩性骨折的效果显著,可改善机体炎性状态,降低术后疼痛程度。     

Regulation of bone cell function by acid-base balance

Bone growth and turnover results from the coordinated activities of two key cell types. Bone matrix is deposited and mineralised by osteoblasts and it is resorbed by osteoclasts, multinucleate cells that excavate pits on bone surfaces. It has been known since the early 20th century that systemic acidosis causes depletion of the skeleton, an effect assumed to result from physico-chemical dissolution of bone mineral. However, our own work has shown that resorption pit formation by cultured osteoclasts was absolutely dependent on extracellular acidification; these cells are inactive at pH levels above about 7.3 and show maximum stimulation at a pH of about 6.9. Bone resorption is most sensitive to changes in H+ concentration at a pH of about 7.1 (which may be close to the interstitial pH in bone). In this region pH shifts of < 0.05 units can cause a doubling or halving of pit formation. In whole-bone cultures, chronic HCO3- acidosis results in similar stimulations of osteoclast-mediated Ca2+ release, with a negligible physico-chemical component. In vivo, severe systemic acidosis (pH change of about -0.05 to -0.20) often results from renal disease; milder chronic acidosis (pH change of about -0.02 to -0.05) can be caused by excessive protein intake, acid feeding, prolonged exercise, ageing, airway diseases or the menopause. Acidosis can also occur locally as a result of inflammation, infection, wounds, tumours or diabetic ischaemia. Cell function, including that of osteoblasts, is normally impaired by acid; the unusual stimulatory effect of acid on osteoclasts may represent a primitive 'fail-safe' that evolved with terrestrial vertebrates to correct systemic acidosis by ensuring release of alkaline bone mineral when the lungs and kidneys are unable to remove sufficient H+ equivalent. The present results suggest that even subtle chronic acidosis could be sufficient to cause appreciable bone loss over time.     

Matrix metalloproteases and their association to tuberculosis

Tuberculosis (TB) remains as the single most relevant bacterial infectious disease worldwide, causing nearly eight million new cases annually, with an estimated death toll close to two million people per year. The World Health Organization estimates that one third of the world population is latently infected with Mycobacterium tuberculosis (Mtb). Latent TB reactivation remains as the most common cause of new cases of active TB, given inflammation, necrosis and pulmonary cavitation lead to tissue erosion and dissemination to uninfected hosts. Current knowledge of events regulating exacerbated inflammatory responses is scarce. However, participation of components from both the infectious agent and the host is suspected. In this regard, likely candidates to participate in cavitation are matrix metalloproteases (MMPs), a family of proteolytic enzymes required for degrading and reconstructing tissue either in normal or pathological conditions, as well as for processing signaling molecules including cytokines and chemokines. Some studies have reported induction of MMPs genes in response to mycobacterial infection in cellular models, or how inhibiting MMPs action modify the course of tuberculosis infection in murine models.     

Low Folate Status Enhanced Benzene-Induced Cytogenetic Damage in Bone Marrow of Mice: A Relationship Between Dietary Intake and Tissue Levels of Folate

We examined the protective effect of dietary folate on benzene-induced chromosomal damage in bone marrow of mice regarding folate levels in diet and tissue. Male mice were fed either a deficient, basal, or high folate diet (0, 2, or 8 mg/kg diet, respectively) for 4 wk followed by a single dose of benzene. Plasma folate levels corresponded to those of dietary intake. Meanwhile, bone marrow, erythrocyte, and liver folate were decreased to 40% in the deficient group and almost saturated in the high group. Plasma homocysteine levels negatively correlated to levels of tissue folate. Chromosomal damage, evaluated by micronucleus assay, was not affected by folate status alone but was markedly enhanced by benzene, particularly in the deficient group (P < 0.05 vs. the basal and high groups). The activities of hepatic drug-metabolizing enzymes did not enhance benzene metabolism in the deficient groups, indicating that enhanced chromosomal damage was solely due to the low folate status. These results suggest that a low folate status can increase the risk of benzene-induced chromosomal damage in bone marrow, but excess folate intake does not enhance protection, as it is saturated in tissue.     

Low folate status enhanced benzene-induced cytogenetic damage in bone marrow of mice: a relationship between dietary intake and tissue levels of folate

We examined the protective effect of dietary folate on benzene-induced chromosomal damage in bone marrow of mice regarding folate levels in diet and tissue. Male mice were fed either a deficient, basal, or high folate diet (0, 2, or 8 mg/kg diet, respectively) for 4 wk followed by a single dose of benzene. Plasma folate levels corresponded to those of dietary intake. Meanwhile, bone marrow, erythrocyte, and liver folate were decreased to 40% in the deficient group and almost saturated in the high group. Plasma homocysteine levels negatively correlated to levels of tissue folate. Chromosomal damage, evaluated by micronucleus assay, was not affected by folate status alone but was markedly enhanced by benzene, particularly in the deficient group (P < 0.05 vs. the basal and high groups). The activities of hepatic drug-metabolizing enzymes did not enhance benzene metabolism in the deficient groups, indicating that enhanced chromosomal damage was solely due to the low folate status. These results suggest that a low folate status can increase the risk of benzene-induced chromosomal damage in bone marrow, but excess folate intake does not enhance protection, as it is saturated in tissue.     

Dose-response study of effect of oleuropein, an olive oil polyphenol, in an ovariectomy/inflammation experimental model of bone loss in the rat

BACKGROUND & AIMS: This study was carried out to assess the dose-dependent bone-sparing effect of oleuropein, an olive oil phenolic compound with anti-inflammatory and anti-oxidative properties, on bone loss induced by talc granulomatosis in oestrogen-deficient rat. METHODS: Among 98 rats, 20 were sham-operated (SH) while the others (78) were ovariectomised (OVX). The SH and 26 OVX rats (controls) were given a standard diet for 100 days. The 52 remaining OVX rats were allocated to 4 groups that received oleuropein at 2.5, 5, 10 or 15 mg/kg body weight per day for 100 days. Three weeks before necropsy, an inflammation was induced by subcutaneous injections of talc in half of the SH and OVX rats and in all oleuropein-treated animals. RESULTS: Castration was associated with a decreased bone mineral density (BMD). In OVX rats, inflammation, characterised by an increase of the spleen weight and plasma fibrinogen levels, exacerbated this bone loss, as shown by values of BMD of the total femur metaphyseal and diaphyseal subregions. The 4 doses of oleuropein reduced bone loss and improved inflammatory biomarkers excepted for 5mg/kg BW. CONCLUSIONS: Every dose of oleuropein elicited protective effects on bone mass in this model of ovariectomy associated with inflammation, probably by modulating inflammatory parameters.     

Carcinogenesis by thorotrast and other sources of irradiation, especially other alpha-emitters.

Carcinogenesis by α-particles has special features. Tissue irradiation is always inhomogeneous, sometimes extremely so. Tissue damage will be focal because cells out of reach of α-tracks (often the majority of cells) will not be irradiated at all. Since it is these unirradiated cells which allow tissue regeneration, random decay of radionuclides is a mechanism which increases nonhomogeneity of distribution of α-emitters in tissue as time progresses. Focal damage implies that cancer induction is linear with dose but, because the length of an α-track in tissue exceeds the dimensions of a single cell, linearity does not necessarily imply that malignant transformation is exclusively an intracellular process. Cellular inactivation of transformed cells will reduce the frequency of observed tumours and is easier to allow for than with low LET radiation because after high LET radiation there is no shoulder on the curve for retention of clonogenicity. With high LET radiation the dose response for carcinogenesis is sublinear, aDe^?bD. When tissue exposures are protracted, cellular inactivation and tissue repopulation by means of cell division will proceed side-by-side throughout the exposure. Cellular repopulation will tend to neutralise the influence of inactivation on tumour frequency so that, as daily dose of protracted exposure decreases, observed tumour frequency may increase and become linear with dose. Human experience of carcinogenesis by α-emitters in bone and lung provides dose-responses compatible with linearity for induction, even in the case of Ra-226. In bone there may be quantitatively important age differences in sensitivity to sarcoma induction. Hepatic carcinogenesis by Thorotrast is an unsatisfactory model for other α-emitters because in virtually all subjects bearing Thorotrast the liver is structurally abnormal as a consequence of tissue damage. The linear risk coefficient for Thorotrast-induced malignant disease originating in bone marrow (mostly leukaemia) and for death from bone marrow failure implies that RBE for comparisons with low LET radiation is small 1–3. This may not be unreasonable since α-irradiation of the marrow will have been largely focal, leaving many marrow cells unaffected. However an alternative possibility is that cellular inactivation has led to a falsely low value for the risk coefficients for α-irradiation by Thorotrast. Deeper understanding of observations on Thorotrast subjects and application of them to problems of human exposure to other α-emitters, such as plutonium, require (a) subdivision of subjects according to volume of Thorotrast injected, so that dose response relationships may be examined directly without reliance on the assumption of linearity, and (b) decisive experiments to show whether chemical toxicity as well as α-radioactivity contributes to tissue damage and induction of cancer.     

The metabolism of proline as microenvironmental stress substrate

Proline, a unique proteogenic secondary amino acid, has its own metabolic system with special features. Recent findings defining the regulation of this system led us to propose that proline is a stress substrate in the microenvironment of inflammation and tumorigenesis. The criteria for proline as a stress substrate are: 1) the enzymes utilizing proline respond to stress signaling; 2) there is a large, mobilizable pool of proline; and 3) the metabolism of proline serves special stress functions. Studies show that the proline-utilizing enzyme, proline oxidase (POX)/proline dehydrogenase (PRODH), responds to genotoxic, inflammatory, and nutrient stress. Proline as substrate is stored as collagen in extracellular matrix, connective tissue, and bone and it is rapidly released from this reservoir by the sequential action of matrix metalloproteinases, peptidases, and prolidase. Special functions include the use of proline by POX/PRODH to generate superoxide radicals that initiate apoptosis by intrinsic and extrinsic pathways. Under conditions of nutrient stress, proline is an energy source. It provides carbons for the tricarboxylic acid cycle and also participates in the proline cycle. The latter, catalyzed by mitochondrial POX and cytosolic pyrroline-5-carboxylate reductase, shuttles reducing potential from the pentose phosphate pathway into mitochondria to generate ATP and oxidizing potential to activate the cytosolic pentose phosphate pathway.     

Tackling tissue destruction in tuberculosis

Drug-resistant tuberculosis (TB) is a major worldwide problem. The immune system usually controls TB, but once active disease develops, the inflammatory immune response drives tissue destruction. Tissue damage is a result of enzymatic activity, and matrix metalloproteinases (MMPs) have a key role. There are a few new anti-mycobacterial drugs in trial and some vaccine candidates in development but options for control of TB are limited. A novel approach may be to combine antibiotic therapy with limiting the activity of the key mediators of tissue damage, such as MMPs, by inhibiting either the enzymes directly or the pathways that regulate them.     

Skeletal malformations induced by the insecticides ZZ-Aphox® and Folidol® during larval development of Rana perezi

Tadpoles of Rana perezi were kept for 14 weeks in water containing two sublethal levels of the carbamate insecticide ZZ-Aphox® or the organophosphate Folidol®. Approximate concentrations of their active ingredients were 0.25 and 1 mg/L. Resulting malformations were studied by skeletal analysis and histological and histochemical investigation of the rear limbs of the tadpoles. The pesticides caused the animals to have malformations of the spinal column (scoliosis) and/or limbs (short and thick long bones with the epiphyses grossly twisted). Histochemical study showed differences in the composition of the connective matrix, and microscopic examination of the long bones indicated alterations in the thickness of the uncalcified bone matrix (osteoid) and the presence of abundant vascularised connective tissue in the region of the periosteum. The results confirmed changes in the composition of the connective tissue matrix as the cause of the defects observed in bone formation which are also discussed in relation to vitamin D absorption and calcium homeostasis.     

Induction of mixed function oxidases by petroleum in the American eel,Anguilla rostrata

American eels,Anguilla rostrata, were exposed to crude oil by ingestion of a 10, 100, or 500 l/kg fish dose per day for five days. Depuration was followed for an additional twelve days. All oil doses caused an induction of hepatic microsomal enzymes, maximally by three days of exposure. Benzo(a)pyrene hydroxylase (BaPH) showed a dose related response, with greater induction at 100 l/kg than at the other doses. The highest dose was hepatotoxic. Cytochrome P-450 induction was dose independent, and remained induced maximally for the entire experimental period, in contrast to BaPH which declined in activity. Reaction optimum for BaPH was at pH 7.5 and 27°C. A study of tissue distribution showed the liver to account for nearly all BaPH activity. A significant increase in the protein content of the hepatic postmitochondrial fraction of oil-exposed fish was also observed.     

山茶籽联合雌二醇对去卵巢大鼠骨重建和骨代谢酶的影响

目的:了解山茶籽联合雌二醇对去卵巢大鼠骨重建和骨代谢酶的影响,为山茶籽联合雌二醇治疗Ⅰ型骨质疏松症提供实验依据。方法:将90只5月龄健康雌性大白鼠分成假手术组(sham)、去卵巢模型组(OVX)、山茶籽组、雌二醇组(E2)、小剂量山茶籽+雌二醇组(Ts+E2),每组各18只。各实验组在第8、12、16周,随机处死6只大鼠,取左股骨切片观察骨组织,取右股骨测量骨密度,取左心血测量血清雌二醇、碱性磷酸酶。数据进行统计学分析。结果:OVX组的血清雌二醇和骨密度明显低于sham组(P<0.01),而血清碱性磷酸酶明显高于sham组(P<0.01);3个治疗组与sham组相比,各时间的血清雌二醇、碱性磷酸酶、骨密度均无显著性差异(P>0.05)。结论:小剂量的雌二醇联合山茶籽对去卵巢大鼠的骨质疏松症的治疗效果与单独使用较大剂量的山茶籽或较大剂量的雌二醇的治疗效果相近。