ω-3多不饱和脂肪酸预处理对创伤性休克大鼠继发性肝损伤的影响

目的 评价ω-3多不饱和脂肪酸(ω-3 PUFA)预处理对创伤性休克大鼠继发性肝损伤的影响.方法 雄性Wistar大鼠48只,3月龄,体重240～260 g,采用随机数字表法,将其随机分为4组(n=12):假手术组(S组)、S+ω-3 PUFA组、创伤性休克组(TS组)和TS+ ω-3 PUFA组.TS+ ω-3 PUFA组与S+ ω-3PUFA组分别于造模前12 h、造模前2h时经尾静脉注射ω-3 PUFA 2 ml/kg,S组和TS组注射等容量生理盐水.建立大鼠股骨骨折合并失血致创伤性休克模型,模型制备成功后2h采集颈动脉血,检测血清ALT、AST活性及8-异前列腺素F2α(8-iso-PGF2α)、TNF-α浓度,随后处死大鼠取肝组织,检测肝组织SOD活性及MDA、谷胱甘肽(GSH)含量,光镜下观察肝组织病理学结果,并进行肝损伤评分.结果 与S组比较,TS组和TS+ω-3 PUFA组血清ALT、AST活性及8-iso-PGF2α、TNF-α浓度升高,肝组织MDA含量升高,SOD活性及GSH含量降低,肝组织损伤评分升高(P＜0.01);与TS组比较,TS+ ω-3 PUFA组血清ALT、AST活性及8-iso-PGF2α、TNF-α浓度降低,肝组织MDA含量降低,SOD活性及GSH含量升高,肝组织损伤评分降低(P＜0.05或0.01).结论 ω-3 PUFA预处理可减轻创伤性休克大鼠继发性肝损伤,与其抑制脂质过氧化反应和炎性反应有关.     

Effects of polyunsaturated fatty acids (PUFAs) in the treatment of experimental chronic renal failure

Purpose

A diet with polyunsaturated fatty acid (PUFA) supplementation has been reported to reduce renal and cardiac diseases. This study sought to elucidate whether PUFAs derived from plant or marine oils could have beneficial effects on the progression of experimental chronic renal failure (CRF).

Methods

Experimental CRF was achieved by a 5/6 nephrectomy model. Male Wistar rats were divided into groups and given daily supplements of fish oil (group FO), flaxseed oil (group FXO), or soybean oil (control?Cgroup SO) for 30?days. Serum creatinine (sCr), 24-h proteinuria, total cholesterol, triglycerides, and creatinine clearance (CLcr) were measured at day 0 and 30?days after surgery when the rats were euthanized for histological analysis of the remnant kidney.

Results

After 30?days, we observed lower levels of sCr in the groups supplemented with PUFA when compared with the control group (FO: 0.92?±?0.13; FXO: 1.06?±?0.28; SO: 1.32?±?0.47?mg/dL) and significantly slower variations of sCr (??sCr) in the groups treated with PUFAs (FO?=?0.35?±?0.16; FXO?=?0.47?±?0.31; OS?=?0.72?±?0.43; mg/dL, P?=?0.041). Similarly, the CLcr of both of the groups that received PUFAs was significantly slower than the rats in the control group (FO: 0.45?±?0.15; FXO: 0.60?±?0.09; SO: 0.28?±?0.06?mL/min/day; P?=?0.01). The rats that received PUFA supplements also presented significantly less histological lesions compared with the control group.

Conclusions

These results suggest a beneficial effect of dietary supplementation with flaxseed or fish oil in rats with CRF.     

ω-3多不饱和脂肪酸联合营养支持治疗在肝切除术后应用的临床研究

目的 通过比较不同营养支持方案的作用,评价ω-3多不饱和脂肪酸联合营养支持治疗在肝切除术后应用的临床效果。方法 采用回顾性对照研究的方法.选择2009年1月-2011年1月南京大学医学院附属鼓楼医院82例行肝切除术患者,依照围手术期不同的营养支持方案分为全肠外营养组（23例,简称肠外组）、联合肠内营养组（30例,简称肠内组）和ω-3不饱和脂肪酸组（29例,简称ω-3 PUFAs组）。肠外组术后给予全肠外营养支持;肠内组在静脉营养支持基础上术后早期口服肠内营养;ω-3 PUFAs组在肠内组基础上,术后加用ω-3多不饱和脂肪酸。通过比较3组患者术后恢复情况、并发症发病率、肝功能等临床指标综合评估不同营养支持方案的疗效。结果 （1）3组患者术后均无胆漏、胆道出血等严重并发症,轻微并发症包括腹腔积液、胸腔积液,3组间差异无统计学意义;（2）与肠外组比较,肠内组、ω-3 PUFAs组术后排便时间、术后住院天数较短,差异有统计学意义（P =0.001,=4.624;P =0.001,t =5.019）;肠内组、ω-3PUFAs组间差异无统计学意义（P＞0.05）;（3）对于大范围（≥4个肝段）肝切除患者,与肠内组相比,ω-3PUFAs组术后第3、5天ALT值较低,差异有统计学意义（P=0.024,t=2.432;P=0.042,=2.144）;（4）对于有肝硬化的患者,与肠内组相比,ω-3 PUFAs组术后第3、5天胆红素值较低,差异有统计学意义（P=0.032,t=2.202;P=0.035,t =2.183）。结论 肝切除术后早期给予肠内营养并联合肠外营养支持,可加速患者康复;对于有肝硬化背景及大范围肝切除的患者,ω-3 PUFAs联合营养支持治疗对肝功能的保护作用尤为明显。     

ω-3多不饱和脂肪酸对创伤性休克大鼠急性肺损伤的影响

目的 探讨ω-3多不饱和脂肪酸(ω-3 PUFA)对创伤性休克大鼠急性肺损伤的影响.方法 雄性Wistar大鼠36只,体重240～260 g,月龄3月,采用随机数字表法,将大鼠随机分为3组(n=12):对照组(C组);创伤性休克组(TS组)采用骨折复合失血致创伤性休克;ω-3 PUFA组于造模前12 h及2 h经尾静脉注射ω-3 PUFA 2 ml/kg,C组和TS组注射生理盐水2 ml/kg.模型制备成功后120 min时采集颈动脉血样,处死取肺组织.用ELISA法检测血清TNF-α、8-异前列腺素F2α(8-iso-PGF2α)、IL-1β及IL-10的浓度;计算肺组织湿/干重比(W/D比);光镜下观察肺组织病理变化,行病理学评分.结果 与C组比较,TS组和ω-3 PUFA组血清TNF-α、8-iso-PGF2α、IL-1β及IL-10的浓度、肺组织W/D比及病理学评分明显升高(P＜0.01).与TS组比较,ω-3 PUFA组血清TNF-β、8-iso-PGf2α及IL-1β的浓度、肺组织W/D比及病理学评分明显降低,血清IL-10浓度升高(P＜0.05或0.01).结论 ω-3 PUFA可有效地抑制创伤性休克大鼠全身炎性反应,减轻急性肺损伤.

Abstract：

Objective To investigate the effects of ω-3 polyunsaturated fatty acid (ω-3 PUFA) on acute lung injury (ALI) in a rat model of traumatic shock. Methods Thirty-six male Wistar rats aged 3 months were randomly assigned into 3 groups ( n = 12 each): control group (group C) ; traumatic shock group (group TS) and ω-3 PUFA + TS group (group to-3 PUFA) . Traumatic shock was induced by fracture of femur and hemorrhage according to the method described by Feeney in groups TS and ω-3 PUFA. In group ω-3 PUFA, ω-3 PUFA 2 ml/kg was injected via the caudal vein at 12 and 2 h before induction of traumatic shock. Arterial blood samples were taken at 120 min after traumatic shock was successfully induced for determination of serum concentrations of TNF-α, IL-1β, IL-10 and 8-iso-PGF2α by ELISA. The animals were then sacrificed and lungs were removed for-determination of W/D lung weight ratio and microscopic examination. Results Traumatic shock significantly increased serum concentrations of TNF-α, IL-1β, IL-10 and 8-iso-PGF2α, W/D ratio and pathologic scores of lung tissues in groups TS and ω-3 PUFA as compared with group C.ω-3 PUFA significantly attenuated traumatic shuck-induced increase in serum concentrations of TNF-α, IL-1β and 8-iso-PGF2α , W/D ratio and pathologic scores of lung tissues but further increased the serum IL-10 concentration in group ω-3 PUFA as compared with group TS. Conclusion ω-3 PUFA can significantly inhibit the svstemic inflammatory response and ameliorate traumatic shock-induced ALI.     

Changes in Bone Mass,Bone Structure,Bone Biomechanical Properties,and Bone Metabolism after Spinal Cord Injury: A 6-Month Longitudinal Study in Growing Rats

Spinal cord injury (SCI) results in a great decline in bone mineral density (BMD) and deterioration of bone microarchitecture. The objective of this study was to investigate the time course of the changes in BMD, microarchitecture, biomechanical properties, and bone turnover in male growing rats following SCI. Sixty male growing Sprague-Dawley rats, 6 weeks of age, were randomly divided into SCI (lower thoracic cord transection) and sham-operated groups, and bone tissues and blood samples were examined at 3 weeks, 6 weeks, and 6 months after surgery. SCI rats had low bone weight (wet, dry, and ash weight) and BMD of the femora, tibiae, and third lumbar vertebrae at all time points compared to sham rats, while in forelimbs, there was a decrease of dry and ash weight compared to sham rats only at 3 weeks but not BMD. Bone microarchitecture and trabecular connectivity were deteriorated in SCI rats and remained so after. Bone formation rate and serum osteocalcin level in SCI rats were significantly increased 3 weeks after SCI surgery. However, eroded surface/bone surface and serum N-terminal telopeptide of type I collagen level remained elevated from 3 weeks to 6 months. In addition, SCI rats showed poor biomechanical properties in the proximal tibiae and femora but not in the humeri. In conclusion, SCI causes profound BMD loss, disturbances in bone microarchitecture, decreased mechanical strength in the lower extremity and lumbar spine, and high bone turnover. These findings will allow better understanding of osteoporosis following SCI.     

Fish-oil emulsion (omega-3 polyunsaturated fatty acids) attenuates acute lung injury induced by intestinal ischemia–reperfusion through Adenosine 5′-monophosphate-activated protein kinase–sirtuin1 pathway

Background

Activated macrophage infiltration into the lungs is paramount in the pathogenesis of acute lung injury (ALI) induced by intestinal ischemia–reperfusion (I/R). Omega-3 polyunsaturated fatty acid (ω-3 PUFA) is a potent activator of the Adenosine 5′-monophosphate-activated protein kinase–sirtuin1 (AMPK/SIRT1) pathway against macrophage inflammation. We aimed to evaluate whether ω-3 PUFAs may protect against ALI induced by intestinal I/R via the AMPK/SIRT1 pathway.

Methods

Ischemia in male Wistar rats was induced by superior mesenteric artery occlusion for 60 min and reperfusion for 240 min. One milliliter per day of fish-oil emulsion (FO emulsion, containing major ingredients as ω-3 PUFAs) or normal saline (control) was administered by intraperitoneal injection for three consecutive days to each animal. All animals were sacrificed at the end of reperfusion. Blood and tissue samples were collected for analysis.

Results

Intestinal I/R caused intestinal and lung injury, evidenced by severe lung tissue edema and macrophage infiltration. Pretreatment with FO emulsion improved the integrity of microscopic structures in the intestine and lungs. Intestinal I/R induced the expression of macrophage-derived mediators (macrophage migration inhibitory factor and macrophage chemoattractant protein-1), inflammatory factors (nuclear factor κB, tumor necrosis factor α, interleukin 6, and interleukin 1β), and proapoptosis factor p66shc. There was a decrease in the expression of AMPK, SIRT1, and claudin 5. FO emulsion significantly inhibited macrophage infiltration into the lungs, inflammatory factor expression, and p66shc phosphorylation. Importantly, FO emulsion restored AMPK, SIRT1, and claudin 5 in the lungs.

Conclusions

Pretreatment with ω-3 PUFAs effectively protects intestinal and lung injury induced by intestinal I/R, reduces macrophage infiltration, suppresses inflammation, inhibits lung apoptosis, and improves the lung endothelial barrier after intestinal I/R in a manner dependent on AMPK/SIRT1. Thus, there is a potential for developing AMPK/SIRT1 as a novel target for patients with intestinal I/R–induced ALI.     

Severe bone alterations under beta2 agonist treatments: bone mass, microarchitecture and strength analyses in female rats

AIMS: Beta2 adrenergic agonists are widely used in therapeutics and as doping agents by athletes. However, their effects on bone tissue, especially bone microarchitecture, remain poorly understood. Using three-dimensional (3D) microtomography, dual-energy X-ray absorptiometry, biomechanical testing and enzyme-linked immunosorbent assay, we evaluated the effects of two beta2 agonists, clenbuterol and salbutamol, on bone in growing rats. METHODS: Twelve-week-old Wistar female rats (N = 39), divided in 3 groups, received during 6 weeks either salbutamol (4 mg/kg/day), clenbuterol (2 mg/kg/day) or normal saline (0.5 ml/kg/day) by subcutaneous injections. RESULTS: After 6 weeks, the salbutamol and clenbuterol groups displayed lower bone mineral content (BMC), femoral length and cortical width than controls. Clenbuterol treatment further reduced bone mineral density. Bone microarchitecture was clearly altered by clenbuterol, as evidenced by lower trabecular number (-40.40%; P < 0.001), connectivity and trabecular bone volume (-42.85%; P < 0.001), leading to lower ultimate force. Clenbuterol significantly increased muscle mass (P < 0.01) and reduced fat mass when compared to controls. Salbutamol did not seem to have any effect on bone microarchitecture or body composition. Both beta2 agonists increased the bone resorption marker (C-terminal collagen crosslinks) without any change of a bone formation marker. At the end of the treatment, a drop in leptin was seen in the clenbuterol group only. Leptin levels were correlated with BMC (r = 0.69, P = 0.003). CONCLUSION: These results confirm the deleterious effect of beta2 agonists on bone mass and show the negative effects of clenbuterol on trabecular bone microarchitecture. Bone loss occurred independently from muscle mass but was related to fat mass. A leptin-mediated effect on bone tissue seems likely. These pathophysiological effects may have important consequences in human therapeutics and doping.     

High linoleic acid diets ameliorate diabetic nephropathy in rats

The value of high polyunsaturated fatty acid (PUFA) diets in preventing diabetic nephropathy in rats was studied. Diabetes was induced by intravenous injection of streptozotocin (SZ), 65 mg/kg. Rats were divided in four groups fed diets containing 11% fat for 38 weeks. Dietary fat derived from four sources: beef tallow (BT; rich in saturated fatty acids), evening primrose oil (EPO; rich in gamma linolenic [GLA] and linoleic acids [LA]), safflower oil (SO; rich in LA), and fish oil (FO; rich in eicosapentaenoic [EPA] and docosahexaenoic [DHA] acids). Ultralente insulin was administered every other day to maintain the blood glucose levels between 11.1 and 22.2 mmol/L (200 and 400 mg/dL). The diets prepared with EPO and SO had a clear beneficial effect on proteinuria, glomerular sclerosis, and tubular abnormalities, as compared with BT. Both diets also increased the ratio of renal cortical production of 6-keto-PGF1 alpha to thromboxane B2 (TXB2), the stable metabolites of PGI2 and TXA2, respectively. They did not induce significant changes in plasma lipid composition. The FO diet did not have an effect on renal disease, but decreased plasma lipids and inhibited eicosanoid synthesis by platelets and kidney cortex. FO feeding was associated with a lowered 6-keto-PGF1 alpha/TXB2 ratio. It is concluded that high LA diets are protective in this model of diabetic nephropathy. The effect may be secondary to modifications of the eicosanoid balance. Diets containing FO have a beneficial effect on plasma lipids in this model.     

Intermittent administration of bovine PTH-(1-34) increases serum 1,25-dihydroxyvitamin D concentrations and spinal bone density in senile (23 month) rats.

We examined the effect of intermittent administration of bovine parathyroid hormone (1-34) (bPTH) on spinal bone mineral content (BMC) and bone mineral density (BMD), serum 1,25-dihydroxyvitamin D concentrations, and serum markers of osteoblast function in senile male and female rats (23 and 24 months of age, respectively). Sexually mature young (3 month) male rats were similarly treated for comparison. bPTH administration increased serum osteocalcin concentrations without changing serum inorganic phosphate or calcium concentrations in either group of old animals. In young animals, PTH administration increased the serum calcium and inorganic phosphate concentrations significantly (p less than 0.05), although values remained within the normal range. In the vehicle-treated male rats, serum 1,25-dihydroxyvitamin D concentrations were lower in the senile than in the young animals (18 +/- 5 versus 47 +/- 6 pg/ml, p less than 0.05). PTH administration resulted in significantly increased serum 1,25-dihydroxyvitamin D concentrations in the senile and young male animals (both, p less than 0.05) and the final mean serum 1,25-dihydroxyvitamin D concentrations were not statistically different (68 +/- 9 versus 85 +/- 6 pg/ml respectively; p = NS). Serum 1,25-dihydroxyvitamin D concentrations were significantly (p less than 0.05) higher in the PTH-treated senile female rats than the sex-matched, vehicle-treated controls. The pretreatment spinal BMC and BMD as assessed by dual-energy x-ray absorptiometry (DEXA) were significantly higher in the senile male animals than in the young animals. Spinal BMC and BMD decreased in the vehicle-treated senile male rats (p less than 0.05) over the 3 weeks of the study despite a gain in weight.(ABSTRACT TRUNCATED AT 250 WORDS)     

间歇皮下注射人甲状旁腺激素不同片段(hFTH1-34及 hFTH1-84)对去卵巢大鼠股骨及腰椎骨量的影响

目的 比较间歇皮下注射人甲状旁腺激素不同片段（hPTH1-34)及（hPTH1-84)对完整雌性（Non-OVX)大鼠和去卵巢（OVX）大鼠股骨及腰椎1－4骨矿物含量（BMC）和骨密度（BMD）的影响。方法 Wistar雌性大鼠176只，分为hPTH1-34和hPTH1-84两大组（各80只及96只），每大组及各自分4组（每组各20只或24只），分别为：两组安慰剂组（未切卵巢及切卵巢）用安慰剂（PBS）进行皮下注射，每周3次，共2周；两组治疗组（未切卵巢及切卵巢）用hPTH1-34或hPTH1-84，皮下注射，每周3次，共2周。结果 1．卵巢切除术后3个月大鼠股骨及腰椎1－4BMC和BMD明显下降；2．两种片段的甲状旁腺激素（hPTH1-34及pPTH1-84)间歇注射均能使Non-OVX大鼠和OVX大鼠股骨及腰椎1－4BMC和BMD较相应对照组明显升高；且腰椎1－4较股骨的BMC和BMD升高更明显；3．OVX大鼠治疗后股骨与腰椎1－4BMC和BMD的升高率较Non-OVX大鼠更明显；OVX大鼠在治疗后股骨及腰椎骨量能恢复到去卵巢前水平；4．hPTH1-34较hPTH1-84更明显的使完整大鼠和OVX大鼠股骨BMC和BMD升高。结论 间歇皮下注射人甲状旁腺激素对大鼠股骨及腰椎骨量均有增高作用，尤其对腰椎的骨量以及对去卵巢大鼠骨量升高作用更明显；hPTH1-34片段对大鼠股骨骨量的增高作用强于hPTH1-84片段。     

ω-3不饱和脂肪酸对大鼠肝切除术后肠屏障的影响

目的 观察ω-3不饱和脂肪酸(ω-3PUFA)对大鼠肝切除术后肠屏障的影响.方法 雄性SD大鼠96只随机分为假手术组(S)、生理盐水组(NS+PH)和大(H+PH)、小剂量(L+PH)ω-3PUFA治疗组(2ml/kg、1 ml/kgω-3PUFA静脉注射+大鼠70%肝切除组).检测肝切除术后1、2、3、5 d谷丙转氨酶(ALT)、谷草转氨酶(AST)、门静脉血中自细胞介素(IL)-6、肿瘤坏死因子(TNF)-α、内毒素(ET)水平的变化以及小肠黏膜的病理形态学改变.结果ω-3PUFA治疗组术后1、2、3 d ALT、AST较生理盐水组有显著下降(P<0.05).术后1、2、3、5 d,ω-3PUFA治疗组门静脉血中TNF-α、IL-6有显著降低,内毒素水平也有显著下降[H+PH组分别为:(69.61±15.65)、(53.20±6.26)、(35.90±9.76)、(31.81±8.96)ng/L,L+PH组分别为:(79.99±8.73)、(56.11±5.69)、(43.46±14.39)、(34.40±4.88)ng/L,P<0.05].病理学检查可见生理盐水组肠上皮黏膜组织形态受损明显,ω-3PUFA治疗组肠上皮黏膜受损较小.结论 围手术期应用ω-3PUFA可能通过减少炎症因子的释放达到保护肠屏障的效果.     

Inulin and fructo-oligosaccharides differ in their ability to enhance the density of cancellous and cortical bone in the axial and peripheral skeleton of growing rats

Although dietary fructans improve calcium absorption and bone mineral content (BMC) in rats, their effect on calcium bioavailability and bone density may vary with their degree of polymerization. Therefore, for a 3-month period, growing rats received either a control diet or a diet enriched with either oligofructose (OLF) or inulin. At sacrifice, body weight, lean body mass and appendicular bone length were similar in the 3 groups. Rats fed fructans had a similar increase in cecal wall weight (30%), but the relative increase in cecal levels of calbinding-9 K was 2 in the OLF group and 4 in the inulin group. Further, the significant decrease in serum levels of type I collagen C-telopeptide was greater in the inulin group (30%) than in the OLF group (16%). The increase in whole-body bone mineral content (BMC) as measured by DXA was greater in the inulin group than in the OLF group but DXA detected an increase in the BMC of excised femurs only in the inulin group. In contrast, pQCT conducted ex vivo detected a significant increase in the area and mineral density (BMD) of the cancellous bone of both the proximal tibia and vertebra in rats fed fructans and the effect of inulin was greater (P < 0.01) than that of OLF (P < 0.05). Further, inulin but not OLF significantly enhanced the BMD of the cortical bone in both appendicular and peripheral sites (P < 0.01) as well as the polar stress/strain index of femurs (P < 0.01). These observations suggest that, although both inulin and OLF both have a positive effect on BMD, the greatest effect of inulin is related to the higher capacity of this fructan to reduce bone resorption. The different anti-resorptive capacity of the 2 fructans might be related to their different impact on calcium absorption and bioavailability since the increase in cecal amounts of calbindin-9 K, a protein known to play an important role in calcium absorption, was greater in rat fed inulin than in rats fed OLF. Although cecal wall hyperplasia may be of concern, it remains to establish whether the positive effect of fructans observed on calcium absorption in humans is also associated with a positive effect on bone mass and/or mineral density.     

ω-3多不饱和脂肪酸对失血性休克复苏后大鼠炎症反应抑制作用

目的:研究在复苏前静脉输注ω-3多不饱和脂肪酸对失血性休克复苏后大鼠全身炎症反应的抑制以及对肺的保护作用。方法:选取健康成年SD大鼠[n=60,(250±30)g],随机分为5组:假手术组、休克组、休克复苏组、ω-6组、ω-3组。氯胺酮腹腔麻醉后,暴露右侧股动静脉并插管,诱导休克,使平均动脉压维持在35～40 mm Hg间,持续60 min。后利用回输1/2失血量的全血和Ringer液进行复苏,复苏过程持续30 min,平均动脉压维持在休克前的90%,ω-6组和ω-3组在复苏前30 min经尾静脉注射脂肪乳和鱼油(0.2 g/kg)。各组分别在复苏后30 min和4 h处死50%大鼠,取血清、肺标本。结果:ω-3组大鼠血清炎症及氧化应激指标、肺组织中炎症因子水平与假手术组无统计学差异,并明显低于其他3组;血清GSH在各组间无统计学差异。ω-3组肺组织病理评分及湿重/干重比明显低于休克组、休克复苏组及ω-6组。结论:复苏前给予ω-3PUFAs制剂能够明显抑制大鼠全身炎症反应,并减轻肺损伤程度。     

Dietary conjugated linoleic acids alter serum IGF-I and IGF binding protein concentrations and reduce bone formation in rats fed (n-6) or (n-3) fatty acids.

A study was designed to examine the effects of dietary conjugated linoleic acid (CLA) on serum concentrations of insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBP) and the relationship of these factors to bone metabolism. Weanling male rats were fed AIN-93G diet containing 70 g/kg of added fat for 42 days. Treatments included 0 g/kg or 10 g/kg of CLA and soybean oil (SBO) or menhaden oil + safflower oil (MSO) following a 2 x 2 factorial design. Serum IGFBP was influenced by dietary polyunsaturated fatty acid (PUFA) type ((n-6) and (n-3)) and CLA (p = 0.01 for 38-43 kDa bands corresponding to IGFBP-3). CLA increased IGFBP level in rats fed SBO (p = 0.05) but reduced it in those fed MSO (p = 0.01). Rats fed MSO had the highest serum IGFBP-3 level. Both (n-3) fatty acids and CLA lowered ex vivo prostaglandin E2 production in bone organ culture. In tibia, rats given CLA had reduced mineral apposition rate (3.69 vs. 2.79 microm/day) and bone formation rate (BFR) (0.96 vs. 0.65 microm3/microm2/day); however, the BFR tended to be higher with MSO. Dietary lipid treatments did not affect serum intact osteocalcin or bone mineral content. These results showed that dietary PUFA type and CLA modulate local factors that regulate bone metabolism.     

Pamidronate prevents bone loss and decreased bone strength in adult female and male rats fed an isocaloric low-protein diet.

Isocaloric dietary protein deficiency is associated with decreased BMD and bone strength as well as depressed somatotroph and gonadotroph axis. Inhibition of increased bone resorption by the bisphosphonate pamidronate in rats fed an isocaloric low-protein diet fully prevents bone loss and alteration of bone strength. INTRODUCTION: Isocaloric dietary protein deficiency is associated with decreased BMD and bone strength as well as depressed somatotroph and gonadotroph axis. This negative bone balance is the consequence of increased bone resorption and decreased bone formation. Whether inhibition of bone resorption could prevent low-protein diet-induced bone loss and alteration of biomechanics is not known. MATERIALS AND METHODS: The effect of the bisphosphonate pamidronate was studied in 5.5-month-old female or 6-month-old male rats pair-fed a control (15% casein) or an isocaloric low-protein (2.5% casein) diet for 19 and 26 weeks, respectively. Pamidronate (0.6 mg/kg) was given subcutaneously 5 days/month for 4 months in female rats or for 5 months in male rats. BMD, microarchitecture, and bone strength were measured at the level of the proximal and midshaft tibia. Urinary deoxypyridinoline excretion, serum osteocalcin, and IGF-I were also measured. RESULTS: The increase in bone resorption in female rats (+100%) and in male rats (+33%) fed a low-protein diet was prevented by pamidronate treatment. The reduced osteocalcin levels observed in rats fed a low-protein diet were further decreased in both female (-34%) and male (-30%) rats treated with pamidronate. The bone turnover decrease induced by pamidronate prevented bone strength reduction, trabecular bone loss, microarchitecture, and BMD alterations induced by the isocaloric low-protein diet. Similar effects were observed at the level of the midshaft tibia. Significant decrease of plasma IGF-I was observed in rats fed a low-protein diet independently of the pamidronate treatment. CONCLUSION: In conclusion, inhibition of increased bone resorption in rats fed an isocaloric low-protein diet fully prevents bone loss and alteration of bone strength.     

基于OPG/RANKL/RANK轴观察加味阳和汤及其拆方对去卵巢骨质疏松大鼠的影响

目的观察加味阳和汤及其拆方对OPG、RANKL、RANK含量的影响,探讨其防治绝经后骨质疏松症可能的作用机制及组方配伍的合理性。方法选取48只雌性SD大鼠,加味阳和汤按君臣佐使关系拆方,将大鼠等量随机分为假手术组(SHAM)、模型组(OVX)、君药+臣药组(A组)、君药+臣药+佐药组(B组)、君药+臣药+佐药+使药组(C组)、戊酸雌二醇组(E2V)。除SHAM组外,均采用去卵巢骨质疏松大鼠模型,干预给药后(灌胃90 d),处死动物后取右侧股骨及胫骨通过双能X射线骨密度仪检测骨密度(bone mineral density,BMD)及骨矿含量(bone mineral content,BMC),取左侧股骨行HE染色观察骨显微结构,检测血清中骨代谢指标ALP、Ca~(2+)、P~(3-)、E2及血清OPG、RANKL、RANK含量。结果与SHAM组相比,OVX组大鼠股骨及胫骨BMD、BMC降低(P0.05),骨小梁变细、间隙增大、结构缺失,血清Ca~(2+)、P~(3-)、E2、OPG水平下降(P0.05),血清ALP、RANKL、RANK水平上升(P0.05);与OVX组比较,除A组大鼠股骨及胫骨BMD、BMC、血清Ca~(2+)、P~(3-)、E2、OPG、RANKL及B组P~(3-)水平无显著差异外(P0.05),各给药组大鼠股骨及胫骨BMD、BMC均显著升高(P0.05),骨小梁增多、间隙减小、结构趋向完整,血清Ca~(2+)、P~(3-)、E2、OPG水平上升(P0.05),血清ALP、RANKL、RANK水平下降(P0.05)。结论加味阳和汤及其拆方通过提高去卵巢骨质疏松大鼠BMD、BMC,降低骨代谢,改善骨显微结构从而发挥治疗作用,调节OPG/RANKL/RANK轴是可能的机制。     

应用pQCT与DXA定量检测去卵巢大鼠股骨近端骨质疏松建模效果的对比研究

目的比较pQCT与DXA定量检测去卵巢大鼠股骨近端骨质疏松的建模效果的能力。方法16只8月龄Wistar雌性大鼠(平均体重350g)随机分为模型组(卵巢切除组)与对照组(卵巢假切除组)。术后3个月,取大鼠左侧股骨。应用肢体计算机断层扫描(pQCT)与双能X线骨密度仪(DXA)对骨质疏松建模效果进行对比研究:(1)确定pQCT与DXA测量精度,即计算重复测量的精度误差;(2)比较应用两种骨密度仪所测得的对照组、模型组的骨密度、骨矿含量、骨几何结构参数及其相关系数。结果(1)pQCT总骨及松质骨体密度的测量精度误差分别为2.27%与2.00%,而DXA骨面密度的测量精度误差为3.36%。(2)模型组pQCT总骨体密度和松质骨体密度分别低于对照组8.2%和15.0%犤(模型组-对照组)/对照组×100%犦,差异有显著性(P<0.01);而模型组DXA骨面密度低于对照组3.0%,差异无显著性(P>0.05)。模型组pQCT总骨骨矿含量低于对照组3.7%,差异无显著性(P>0.05),而松质骨骨矿含量低于对照组11.4%,差异有显著性(P<0.05);模型组DXA骨矿含量低于对照组3.0%,差异无显著性(P>0.05)。(3)DXA骨矿含量与pQCT总骨骨矿含量之间呈正相关(r=0.82,P<0.001);DXA骨投影面积与pQCT骨体积之间亦呈正相关(r=0.52,P<0.05);DXA骨面密度与pQCT总骨体密度之间无相关关系(r=0.14,P>0.05)。DXA     

Cortical bone is more sensitive to alcohol dose effects than trabecular bone in the rat

ObjectiveWhile chronic alcohol consumption is known to decrease bone mineral content (BMC), bone mineral density (BMD), and negatively modify trabecular bone microarchitecture, the impact of alcohol on cortical microarchitecture is still unclear. The aim of this study was to investigate the effects of various doses of alcohol on bone density, trabecular and cortical parameters and bone strength in rats.MethodsForty-eight male Wistar rats were divided into four groups: control (C), alcohol 25% v/v (A25), alcohol 30% v/v (A30) and alcohol 35% v/v (A35). Rats in the alcohol groups were fed a solution composed of ethanol and water for 17 weeks while the control group drank only water. Bone quality and quantity were evaluated through the analysis of density, trabecular and cortical bone microarchitectural parameters, osteocalcin and N-Telopeptide concentrations and a 3-point bending test.ResultsBone density along with trabecular and cortical thickness were lower in alcohol groups compared to C. BMD was lower in A35 vs. A30 and cortical thickness was lower in A35 vs. A25 and A30. Pore number was increased by alcohol and the porosity was greater in A35 compared to C. N-Telopeptide concentration was decreased in alcohol groups compared to control whereas no differences were observed in osteocalcin concentrations. Maximal energy to failure was lower in A25 and A35 compared to C.ConclusionChronic ethanol consumption increases cortical bone damage in rats and may have detrimental effects on bone strength. These effects were dose-dependent, with greater negative effects proportionate to greater alcohol doses.     

A comparative study of tissue ω-6 and ω-3 polyunsaturated fatty acids (PUFA) in benign and malignant pathologic stage pT2a radical prostatectomy specimens

ObjectiveTo analyze different polyunsaturated fatty acid (PUFA) tissue levels in malignant compared with benign prostatic tissue from the same prostate specimens.Materials and methodsFresh frozen benign and malignant prostatic tissue was obtained from radical prostatectomy specimens in 49 men with pathologic stage pT2a prostate cancer. Histopathologic examination confirmed that all tissues from each prostate being analyzed were either completely benign or almost totally malignant. The PUFA composition in these tissues was determined by gas-liquid chromatography on a capillary column. The relative amount of each PUFA (% of total fatty acids) was quantified by integrating the area under the peak and dividing the result by the total area of all fatty acids.ResultsTissue levels of dihomo-γ-linolenic acid, (C20:3w6), an ω-6 PUFA and a major precursor of ω-6 PUFA metabolites, were significantly higher in malignant compared with benign tissues (P = 0.002). Tissue levels of the downstream ω-6 metabolites, arachidonic acid (AA) (20:4ω6), and adrenic acid, (22:4ω6), were significantly lower in cancer tissues, (P < 0.0001 and P = 0.013, respectively). Overall, the total levels of ω-6 PUFA were lower in cancer (P = 0.001).ConclusionWe found that the ω-6 PUFA AA and adrenic acid are decreased in malignant prostatic tissues compared with benign tissues from the same prostates. These findings provide additional evidence that dietary fat is associated with prostatic carcinogenesis.