Use of hormonal parameters of phospho-calcium metabolism as a means of discriminating bone and joint disorders in patients with renal insufficiency

Serum carboxyterminal parathyroid hormone (PTH) concentration (homologous measurement of the 53-84 fragment and heterologous bovine measurement) has been measured and correlated with both clinical and radiological findings of secondary hyperparathyroidism (HPT), studied quantitatively according to a score published in literature, in 95 patients with chronic renal failure on maintenance hemodialysis. Mean serum PTH concentration (53.84) is statistically higher in patients with severe clinical and radiological evaluation of HPT than in patients with moderate or slight manifestations of HPT (M +/- DS: 515.8 +/- 243.7 pg/ml VS 271.3 +/- 166.1 pg/ml p less than 0.001). However, even with high serum concentration, serum PTH level does not allow to predict HPT severity, suggesting a retention of PTH fragments in serum without biologic activity probably.     

Calcium and phosphorus deficiency in rats: effects on PTH and 1,25-dihydroxyvitamin D3.

Weanling male Holtzman rats were fed calcium.deficient, phosphorus-deficient, or control diets for 8 wk. Parathyroid hormone (PTH) was measured by radioimmunoassay, and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) by a competitive binding assay. Rats fed the calcium-deficient diet (0.01% calcium, 0.6% phosphorus) became mildly hypocalcemic after 6 days. Serum calcium levels reached 5.5 +/- 0.4 mg/dl (mean +/- SD) in 5 wk (control 10.3 +/- 0.4 mg/dl). PTH increased from 285 +/- 112 to 3658 +/- 428 pg/ml within 6 wk. Maximum serum levels of 1,25(OH)2D3 (111.8 +/- 17.3 vs. control 11.4 +/- 3.8 ng/dl) were reached at 3 wk and thereafter declined to 44.6 +/- 14.0 ng/dl. In rats fed the phosphorus-deficient diet (0.6% calcium, 0.04% phosphorus), serum phosphorus fell within 24 h from 9.1 +/- 0.6 to 3.2 +/- 0.1 mg/dl, recovered to 5.6 +/- 0.4 mg/dl for 2-3 days, and then declined again. Serum calcium reached a maximum of 14.4 +/- 0.4 mg/dl at day 2 (control 10.8 +/- 0.5 mg/dl) and then slowly declined. PTH decreased within 24 h from 243 +/- 59 to 36 +/- 0 pg/ml in phosphorus-depleted rats. Serum levels of 1,25(OH)2D3 increased within 24 h and remained elevated after 6 wk of phosphorus deprivation (61.2 +/- 11.7 ng/dl vs. control 18.3 +/- 0.4 ng/dl).     

Improvement in histological diagnosis of primary hyperparathyroidism with a monoclonal antiparathyroid antibody

The monoclonal antiparathyroid antibody E11 reacts with a glycoprotein of high molecular weight, which acts as a calcium receptor on the surface of parathyroid cells and mediates calcium regulation of parathyroid hormone (PTH) release. Reduced expression of the calcium receptor has been implicated as a cause of the defect in PTH regulation in the pathological parathyroid parenchyma of patients with hyperparathyroidism (HPT). The present study evaluated the efficacy of immunostainings with the E11 antibody in comparison with routine histopathological methods including staining by the oil red O technique for histological discrimination between normal and pathological parathyroid glands. Parathyroid tissue from euparathyroid individuals invariably presented intense and homogeneous surface staining, with the antibody on virtually all chief cells, while the pathological glands from patients with HPT consistently showed heterogeneous and reduced immunostaining. Even minimally enlarged pathological glands from individuals with mild hypercalcemia and the normal-sized glands associated with adenomas displayed parathyroid chief cells with reduced antibody reactivity. The monoclonal antiparathyroid antibody should constitute a useful tool in parathyroid histopathology not only by its ability to identify the parathyroid tissue, but also by directly demonstrating the functionally normal and abnormal cells within the parathyroid tissue.     

分化型甲状腺癌术后^（131）I清甲治疗对甲状旁腺功能的影响

目的：观察分化型甲状腺癌切除术后131I清甲治疗对甲状旁腺功能的影响。方法：：对174例（女116,男58）分化型甲状腺癌术后行131I清甲治疗的患者行血清甲状旁腺素（parathyroid hormone,PTH）检测,平均年龄（43.50±14.02）岁。血清PTH检测分四个阶段进行,分别为首次131I清甲治疗前（阶段Ⅰ）,首次131I清甲治疗后3个月（阶段Ⅱ）、6个月（阶段Ⅲ）和9个月（阶段Ⅳ）。174例患者均于阶段I检测后第2d行首次131I清甲治疗,61例患者于阶段Ⅳ检测后第2d行再次131I治疗。血清PTH测定均采用放射免疫分析,正常值为（5～20）ng/dl,PTH检测值低于5ng/dl认定为甲状旁腺功能减退,PTH检测值低于正常范围持续时间超过6个月,认定为持续性甲状旁腺功能减退,6个月内恢复正常,则认定为暂时性甲状旁腺功能减退。每个阶段中发现的甲状旁腺功能减退病例均以病例数（n）和发生率（%）表示,各阶段中PTH检测值均以x珋±s表示,各阶段间PTH值比较采用ANOVA分析,P〈0.05认为差异有统计学意义。结果：①阶段Ⅰ～Ⅳ中各发现68例（39.08%）,26例（14.94%）,16例（12.50%）和13例（15.12%）甲状旁腺功能减退。持续性甲状旁腺功能减退共发现2例,均产生于阶段Ⅰ。②阶段Ⅰ～Ⅳ所发现的甲状旁腺功能减退患者的PTH检测值分别为2.38±1.39,1.94±1.16,2.10±1.29和2.44±1.20ng/dl。经ANOVA分析,各阶段间PTH水平无明显统计学差异,F=0.863,P〉0.05。结论：分化型甲状腺癌切除术后131I清甲治疗会导致甲状旁腺功能减退,其发生可能与残余甲状腺内放射性131I对甲状旁腺产生的辐射损伤有关,其程度与手术所引起的无明显差异,其发生时间在131I清甲治疗后的较长时间内都有可能发生。所以,分化型甲状腺癌术后患者在131I清甲治疗后应定期复查血清PTH,以期及时发现甲状旁腺功能减退。     

Age-related change in parathyroid hormone-dependent cyclic AMP formation in rat kidney

Parathyroid hormone (PTH) dependent cyclic AMP (cAMP) accumulation was evaluated in renal cortex from 2- and 12-month-old rats. Basal cAMP was lower, and responses to PTH were greater at all concentrations of hormone in kidney from 2-month-old rats. This difference was obliterated by prior removal of parathyroid glands, cAMP responses to calcitonin and both basal and hormone-stimulated adenylate cyclase activity were the same at both ages. The results suggest progressive loss of responsiveness to PTH with age, but at a site other than the receptor—adenylate cyclase complex. Blunted cAMP accumulation in year-old rats most likely reflects agonist-specific desensitization.     

MIB-1 and PCNA immunostaining as a diagnostic adjunct to cervical Pap smear

The present study was done to determine the role of MIB-1 (Molecular Immunology Borstel) and proliferating cell nuclear antigen (PCNA) proliferative index as a diagnostic adjunct to cervical Papanicolaou (Pap) smear for the identification of ascending grades of cervical intraepithelial neoplasia (CIN) developing into cancer in the human uterine cervix. A total of 49 adequate Pap smears with consensus diagnosis were destained for immunocytochemical staining (MIB-1 and PC10). Staining was done by streptavidin-biotin method after antigen retrieval. MIB-1 and PC10 labeling index (LI) were calculated in each case and divided into three groups, i.e., <10%, 10-20%, and >20%, respectively. Statistical analysis was done by using the SPSS 10.0 package. The comparisons were made using analysis of variance (ANOVA) and independent sample t-test. Bivariate and Pearson's correlation coefficient were used to obtain correlations between different groups. Out of 49 cases, 40 cases (81.6%) showed positive immunostaining with MIB-1 and PCNA. Proliferative LI of MIB-1 and PCNA increased with the ascending grades of CIN lesions to carcinoma. The highest proliferative index (mean +/- SD) for PCNA and MIB-1 were observed for the carcinoma group (PCNA LI, 39.200 +/- 1.6865; MIB-1LI, 35.300 +/- 1.8886). A significant positive correlation between ascending grades of squamous intraepithelial lesion (SIL) and labeling indices of markers (r = 0.87 for MIB-1 and r = 0.88 for PCNA) suggests that MIB-1/PCNA proliferative markers can be used as an adjunct to cytomorphological interpretation of conventional cervical Pap smear.     

Fluoride interactions with stimulus-secretion coupling of normal and pathological parathyroid cells.

Effects of the GTP binding protein (G-protein) activator NaF on parathyroid hormone (PTH) release, cytoplasmic Ca2+ concentration ([Ca2+]i) and cAMP content of bovine as well as normal and pathological human parathyroid cells were studied using precautions to avoid CaF2 precipitation. In 0.5 mM external Ca2+, NaF inhibited PTH release and lowered the cAMP content by 50-70% of the effects attained with 3.0 mM Ca2+. The NaF-induced increase of [Ca2+]i was considerably smaller than that obtained with rise of external Ca2+. It seems likely that NaF activates the inhibitory G1-protein involved in the regulation of cAMP generation. However, it is unclear whether the sluggish rise of [Ca2+]i induced by NaF is due to a direct effect of a G-protein on Ca2+ entry, or somehow related to the G-protein mediated formation of inositol 1,4,5-trisphosphate, which is part of the signal transduction pathway normally initiated by Ca2+ binding to its receptor on the parathyroid cell surface. Inhibition of PTH release by NaF probably results from the combined effects on [Ca2+]i and cAMP content. In hyperparathyroidism (HPT) the actions of NaF were not markedly affected despite severe impairments of Ca(2+)-inhibited PTH release and Ca2+ triggered increase of [Ca2+]i. Consistent with observations of down regulation of the parathyroid Ca2+ receptor in HPT, the present results indicate that the disease perturbs signal transduction at a level proximal to the site of action for NaF.     

Regulation of renal adenylate cyclase by parathyroid hormone

This study reports the effects of the removal of endogenous PTH by thyroparathyroidectomy (TPTX) on the recovery of the reduced renal cAMP response to parathyroid hormone (PTH) in rats with chronically elevated PTH secondary to diets deficient in either vitamin D or calcium. After TPTX and infusion with a calcium-glucose solution of the vitamin D-deficient rat, calcium and PTH fell from 5.8 mg/dl and 2,509 pg/ml, respectively, to 4.8 mg/dl and 160 pg/ml at 48 h. There was a partial restoration of response to PTH, assessed by assay of renal cortical adenylate cyclase activity from 64% of control activity prior to TPTX to 84% of control activity at 48 h. When rats fed the diet deficient in calcium were TPTX, serum PTH fell rapidly from 2,811 to 200 pg/ml at 5 h with no further change at 21 h, whereas calcium did not change (5.3 mg/dl). PTH-dependent adenylate cyclase activity increased from 59% of control activity prior to TPTX to 87% at 5 h and 100% of control activity at 21 h after TPTX. Each diet produced similar increases in the serum level of immunoreactive PTH, and the rate of disappearance of the circulating hormone after TPTX was also similar for both groups of rats. The data indicate a slow, partial recovery of the enzyme response to PTH after TPTX of the vitamin D-deficient rat over the time period studied, whereas the recovery was rapid and complete in rats fed the diet deficient in calcium.     

Tumors of the parathyroid gland and circulating parathyroid hormone-related protein associated with persistent hypercalcemia

Neoplasms of the parathyroid glands are uncommon in all species of laboratory and domestic animals, but occur in low incidence in rats, Syrian hamsters, and dogs and rarely in mice. Proliferative lesions of the parathyroid gland include hyperplasia (diffuse and focal), adenomas, and carcinomas. The tumors may be functional or nonfunctional. Trophic atrophy of remaining parathyroid tissue is present around functional tumors. Humoral hypercalcemia of malignancy (HHM) is a syndrome that occurs in human and animal patients with certain malignant neoplasms and is characterized by hypercalcemia, hypophosphatemia, and increased osteoclastic bone resorption. The syndrome is thought to be due to the release of parathyroid hormone (PTH)-like factors by the tumor cells which bind to PTH receptors in bone and kidney and result in the clinical manifestations of HHM. Parathyroid hormone-related protein (PTHrP) is a newly purified and sequenced protein which originated from human tumors associated with HHM. PTHrP has been shown to stimulate in vitro and in vivo effects similar to PTH-like proteins isolated from tumors associated with HHM. Well characterized animal models of HHM include a rat Leydig cell tumor line (Rice-500), the rat Walker mammary carcinosarcoma, and the canine apocrine adenocarcinoma. All 3 models have been found to contain 3 biologic activities which are thought to be important in the pathogenesis of HHM, viz., in vitro bone resorbing activity, adenylate cyclase-stimulating activity of bone and kidney cells, and transforming growth factor activity. The first 2 activities are due to PTH-like proteins which are able to compete for binding to the PTH receptor. The complete spectrum of functional disturbances in patients with HHM may be the result of the combined effects of a PTH-like protein (i.e., PTHrP) and transforming growth factors.     

Clinical studies on phosphate handling in hypercalcaemia

Phosphate indices (serum phosphate, tubular reabsorption of phosphate, renal threshold phosphate concentration (TmP/GFR) and index of phosphate excretion) were studied in 88 hypercalcaemic subjects: 64 with primary hyperparathyroidism (HPT) and 24 with hypercalcaemia from other causes, predominantly malignant disease. HPT patients as a group could easily be separated from normal subjects (n = 16) and patients with functional hypoparathyroidism (n = 7) by use of the phosphate variables but these indices were of little discriminating value for the differential diagnosis between HPT and hypercalcaemia from other causes. There was no difference in the urinary cyclic adenosine monophosphate (cAMP) excretion between the two hypercalcaemic patient groups, but HPT patients had clearly elevated serum parathyroid hormone (PTH) levels compared with normal PTH concentrations in patients with other causes of hypercalcaemia. A positive correlation between cAMP and serum calcium and an inverse relationship between cAMP and TmP/GFR were found in patients with hypercalcaemic malignant disease. These findings suggest the existence of a humoral factor with PTH-like effects in malignant disease. Since PTH levels were low, the physiological actions were apparently not mediated by circulating PTH. No difference in the values for phosphate variables, PTH, cAMP or serum calcium was found between renal stone-forming and stone-free patients with HPT.     

The effect of cimetidine on parathyroid function and histopathology in primary hyperparathyroidism

Recent evidence suggests that cimetidine given pre-operatively in primary hyperparathyroidism (1 degree HPT) might cause structural changes in parathyroid glands, while its suppressive effects on the disease are disputable. To determine these possible changes we studied 38 patients with 1 degree HPT who underwent parathyroidectomy. In 14 of these (group I) cimetidine was given pre-operatively (1000 mg orally daily for 4 weeks). The remaining 24 patients (group II) did not take any drug. Parathyroid function was estimated by nephrogenous cAMP (NcAMP) and serum immunoreactive parathyroid hormone (iPTH) measurements. Histological examination of the parathyroids was made by conventional techniques. In group I at the end of cimetidine treatment, the only change observed was a small but significant (p less than 0.05) decrease of plasma calcium (-0.77 mg/dl). Histologically, the glands of group I--compared with those of group II--showed the following findings: increased gland mass: mean increase 1050 mg (adenomas) and 700 mg (hyperplasias); central oedema in all the cases of group I only; increased (about 50 per cent) cellular size and intranuclear 'inclusions' in 10 out of 14 cases of group I only. It is concluded that treatment with cimetidine in 1 degree HPT is followed by histopathologic alterations leading to increased size of the diseased parathyroids.     

Chronic nephropathy in ad libitum overfed Sprague-Dawley rats and its early attenuation by increasing degrees of dietary (caloric) restriction to control growth

The early development and progression of chronic nephropathy and its amelioration by moderate and marked dietary restriction (DR) was determined in Sprague-Dawley (SD) rats at 20, 33, 60, and 113 weeks of age. Both sexes of SD rats were overfed ad libitum (AL) or DR-fed at 72-79%, 68-72%, or 47-48% of the adult AL intake. The AL-fed rats rapidly developed increased body and kidney size, increased glomerular area (GA) and urinary protein loss, followed by declining creatinine clearance. Early increased kidney growth and glomerular hypertrophy by 20 weeks preceded increases in glomerular sclerotic index (GSI), 7-day BrdU tubular labeling index (TLI), and the lesions associated with chronic nephropathy. The glomerular number (GN) or the number of nephrons did not differ between the groups over the course of the study. Moderate DR (68-79% of AL) prevented the increased kidney size and GA at 20 weeks and delayed increases in GSI and TLI until 60 weeks of age. Marked DR (47-48% of AL) prevented increases in kidney size, GA and TLI at 20 weeks, and GSI at 60 weeks of age. In AL-fed rats, the early increase in GA predicted the early onset of proteinuria and the later decrease in creatinine clearance, and increased GSI, TLI, and mortality from severe nephropathy. The temporal and dose-related effects of increasing degrees of DR demonstrated that while nephron numbers were unchanged with age, the early development of glomerular hypertrophy was the critical morphological biomarker predicting the progression and severity of chronic nephropathy. Caloric restriction by DR prevented or delayed the development of glomerulosclerosis, tubulointerstitial damage, functional changes, morbidity, and mortality associated with chronic nephropathy in AL-overfed SD rats by controlling initial body and kidney growth, glomerular size, and nephron hypertrophy. These results indicate that control of body and renal growth by DR may be essential to prevent the development and progression of glomerulosclerosis in spontaneous nephropathy of laboratory rats.     

Parathyroid carcinoma in multiple endocrine neoplasm type 1 syndrome: case report and systematic literature review

The aim of this report was to illustrate a case of parathyroid carcinoma (PC) in a patient with multiple endocrine neoplasia type 1 (MEN1) along with a comprehensive literature review. A 61-year-old man presented with 9-cm PC causing primary hyperparathyroidism (PHPT). His pre-operative corrected calcium and intact PTH serum levels were 2.92 mmol/L and 391.7 pg/mL, respectively. The neoplastic gland was removed in bloc with thyroid and central compartment lymph nodes. A literature review was run by searching PubMed MEDLINE from 1977 to 2018 for studies of all types, in the English language only, using the terms “Parathyroid, carcinoma, Multiple endocrine neoplasia, type 1, (MEN1).” Pathology confirmed PC. Post-operative calcium and PTH levels were normal. A diagnosis of MEN1 was established post-operatively. Seventeen cases of PC in patients with MEN1 have been reported in the literature. 59% of patients were men, and median age at diagnosis was 50 years, with median serum PTH of 379 pg/mL and median serum calcium level of 3.2 mmol/L. The occurrence of PC in the context of MEN1 is extremely rare. Diagnosis and treatment may represent a challenge, so opportune identification or suspicion of malignancy and adoption of correct surgical approach may offer affected patients the best outcome.     

In situ correlation of synthesis and storage of parathormone in parathyroid gland disease

The distribution and expression of parathyroid hormone (PTH) were investigated in normal and abnormal parathyroid tissue. PTH was detected using a monoclonal antibody with specificity for the 44–68 region of the PTH molecule. Prominent reactivity for PTH was seen in normal parathyroid with a granular pattern of staining. Active parathyroid tissue (adenoma and hyperplasia) showed much less reactivity for PTH, although there was prominent reactivity in the normal tissue around adenomas. Comparison of expression of PTH with that of parathormone mRNA showed a reciprocal pauern in normal tissue and, to a less marked extent, in abnormal tissue. Parathyroid carcinoma in particular had coinciding areas of PTH and PTH mRNA expression. Oxyphil cells had little or no PTH expression, except in the associated ‘colloid’ in some cases. The findings indicate an inverse relationship between storage and cellular synthesis of PTH, this being more marked in physiological than in pathological conditions of the parathyroid.     

Effects of aging on parathyroid hormone stimulated ionic fluxes in rat parotid cell aggregates

The effects of aging on parathyroid hormone stimulated calcium and phosphate efflux from isolated rat parotid cell aggregates differed from that of epinephrine stimulated calcium efflux in magnitude, chronology, and ionic dependence. Parathyroid stimulated ionic fluxes were maximal at 1-3 months of age, declined until 12 months and remained constant thereafter. Epinephrine stimulated calcium efflux remained maximal between 3 and 12 months and declined until at least 24 months. Absolute stimulation of calcium efflux over basal levels was maximal at 4-8% while phosphate efflux was 20-30%.     

Long-term therapy with paricalcitol for secondary hyperparathyroidism in hemodialysis patients

PURPOSE: The efficacy of the vitamin D analog paricalcitol has mainly been shown in short-term studies. There are limited data regarding long-term treatment with this agent. This purpose of this study was to determine long-term effects of paricalcitol therapy on parathyroid hormone (PTH) suppression and serum levels of calcium, phosphorus and calcium-phosphorus product (Ca x P). PATIENTS AND METHODS: Patients who received paricalcitol for > or = 3 months had the following data collected: demographics, drug dosage, serum PTH, corrected serum calcium concentration, serum phosphorus concentrations and serum Ca x P values. RESULTS: Sixteen patients received paricalcitol for a mean of 18 months. The mean +/- SD dose of paricalcitol was 0.13 +/- 0.12 mcg/kg. The mean +/- SD pre-paricalcitol serum PTH concentration was 705 +/- 423 pg/mL. PTH concentration did not change significantly over the duration of treatment (mean +/- SD: 821 +/- 480 pg/mL). The number of patients who had at least one corrected serum calcium concentration > or = 11.5 mg/dL, one serum phosphorus concentration > or = 6.5 mg/dL, or one Ca x P level > or = 70 were 75%, 94% and 82%, respectively. Hypercalcemia and elevated Ca x P value resulted in a mean of 17% of doses being withheld during therapy. CONCLUSION: During the study, PTH was not adequately suppressed by paricalcitol. This was primarily attributed to withholding paricalcitol doses due to elevated serum calcium and Ca x P levels.     

The two-hit theory of neoplasia: implications for the pathogenesis of hyperparathyroidism

Knudson's two-hit or two-mutational-event hypothesis for the initiation of neoplasia suggests that two somatic mutations are necessary for initiation of sporadic neoplasms, and that a genetic plus a somatic mutation are required for hereditary neoplasms. Glucose-6-phosphate dehydrogenase (G6PD) studies of parathyroid tumors of 11 heterozygotes with hyperparathyroidism (HPT), including one with hereditary HPT, have shown both A and B isoenzymes. These findings suggest multicellular development of parathyroid tumors and are compatible with tumors being manifestations of either nonneoplastic hyperplasia or a genetic first mutational event. Parathyroid carcinoma may be the result of a second mutation in cells made susceptible by previous genetic or somatic mutations. Comparison of parathyroid cancer in families with hereditary HPT with sporadic cases from the literature reveals a generally younger onset with hereditary HPT compatible with the two-hit theory. Consideration of these age-of-onset and G6PD findings suggest that hyperparathyroidism may result from either non-neoplastic or mutational-induced processes even though no histologic distinctions have been observed in the hyperplasia associated with these processes.     

胆道外引流对大鼠肝再生的影响及其细胞周期调控机制

目的: 观察胆道外引流(ED)对大鼠肝再生及肝细胞周期的影响。方法: 采用大鼠70％肝切除模型,SD大鼠随机分成6组,每组8只,分别为正常切肝24 h组、48 h组,阻塞性黄疸(OJ)切肝24 h组、48 h组,OJ后ED 3 d切肝24 h组、48 h组。采用增殖细胞核抗原(PCNA)标记和Feulgen染色测定肝再生能力;采用RT-PCR 测定肝组织肝细胞生长因子(HGF)、p27和cyclin D1 mRNA水平变化;免疫组化法测定HGF、转化生长因子β₁(TGF-β₁)和p21在肝细胞的表达。结果: OJ切肝后PCNA标记指数较对照组低(P<0.05),ED后PCNA标记指数更低,与OJ组对比差异显著(P<0.05)。DNA含量变化与PCNA标记指数相似。与正常切肝组比较,OJ后切肝组HGF mRNA下降(P<0.05),ED后切肝组进一步下降并较OJ组低(P<0.05)。与正常组相比,OJ后切肝24 h和48 h cyclin D1 mRNA均下降(P<0.05,P<0.01),ED后切肝组进一步下降,但差异不显著。与正常切肝组相比,48 h时OJ后切肝组高于正常切肝组(P<0.05),ED后p27 mRNA水平较OJ进一步升高(P<0.05)。与正常切肝组比较,OJ后切肝组肝细胞HGF表达在24 h下降(P<0.05),ED后切肝组进一步下降并较OJ组低(P<0.05)。p21表达各组间无显著差异。与正常切肝组相比,24 h时OJ后切肝组TGF-β₁表达上调,差异显著(P<0.05),ED后切肝组上调,但差异不显著。结论: OJ可造成大鼠肝再生能力下降,ED后其肝再生能力进一步降低。ED后肝再生能力下降可能和HGF、p27密切相关,与TGF-β₁、p21、cyclin D1无关。