2.Clinical implication of urinary protein markers in diabetic nephropathy and interventional effects of Chinese herbal medicine.
Xi-Miao SHI ; Xian-Jie MENG ; Yi-Gang WAN ; Shan-Mei SHEN ; Xun-Yang LUO ; Liu-Bao GU ; Jian YAO
China Journal of Chinese Materia Medica 2014;39(14):2589-2594
In clinic, some urinary protein makers can dynamically and noninvasively reflect the degree of renal tubular injury in patients with diabetic nephropathy (DN). These urinary biomarkers of tubular damage are broadly divided into two categories. One is newfound, including kidney injury molecule-1 (Kim-1), neutrophil getatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP) and cystatin C (CysC); the other one is classical, including beta2 microglobulin (beta2-MG), retinal binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG). It is reported that, the increases in urinary protein markers are not only closely related to the damage of tubular epithelial cells in DN patients, but also can be ameliorated by the treatment with Chinese herbal compound preparations or Chinese herbal medicine. Recently, although urinary proteomics are used in the protein separation and identification, the traditional associated detection of urinary protein markers is more practical in clinic. At present, it is possible that the associated detection of urinary biomarkers of glomerular and tubular damages may be a feasible measure to reveal the clinical significance of urinary protein markers in DN patients and the interventional effects of Chinese herbal medicine.
Biomarkers
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urine
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Diabetic Nephropathies
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complications
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drug therapy
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urine
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Drugs, Chinese Herbal
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pharmacology
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therapeutic use
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Humans
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Medicine, Chinese Traditional
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methods
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Proteinuria
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complications
3.Characteristic of urinary protein spectrum in patients with stage III diabetic nephropathy and its regression analysis with traditional Chinese medicine symptom.
Yi-Gang WAN ; Xian-Jie MENG ; Shan-Mei SHEN ; Xun-Yang LUO ; Liu-Bao GU ; Xi-Miao SHI ; Jian YAO
China Journal of Chinese Materia Medica 2013;38(23):4157-4163
To analyze the characteristic of urinary protein spectrum in patients with stage III diabetic nephropathy (DN) and its compliance with traditional Chinese medicine (TCM)symptom, for the sake of providing a basis for clarifying the rules of TCM syndrome differentiation in DN. Adopting the traditional epidemiological retrospective method, thirty-eight TCM syndromes and urinary protein with medium or low molecular weight, as well as urinary enzyme, including 24 h urinary protein (Upro), urinary albumin( UAlb), urinary retinal binding protein( URBP), urinary cystatin C (UCysC), urinary N-acetyl-beta-D-glucosaminidase (UNAG), were collected from 108 patients with stage III DN, and a multiple factor regression analysis between them was conducted. As the results, the levels of Upro, UAlb, URBP, UCysC, and UNAG were increased in 108 patients with stage III DN. Qi-Yin deficiency type was the major type. The level of UAlb in patients with Qi-Yin deficiency type was significantly higher than those without Qi-Yin deficiency type (P < 0.05). The elevation of Upro with the factors as swift digestion with rapid hungering, lassitude and lack of strength, weakness of waist and knees was complied, the elevation of UA1b with the factors as dry mouth with desire to drink, the elevation of URBP with the factors as numbness of extremities, shortness of breath, the elevation of UCysC with the factors as clear urine in large amounts, and the elevation of UNAG with the factors as frequent micturition, were complied respectively. In conclusion, for 108 stage III DN patients. The increase in urinary protein spectrum including UAlb, URBP, UCysC, and UNAG is the major characteristic. Shen and Pi are the major organs related to the appearance of urinary protein; Pi-Shen deficiency is the basic pathogenesis. The level of UAlb is taken as one of the objective syndrome factors for Qi-Yin deficiency type. The levels of UNAG and UCysC are possibly the objective syndrome factors for Shen-Qi deficiency type.
Diabetic Nephropathies
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complications
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diagnosis
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urine
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Female
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Humans
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Male
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Medicine, Chinese Traditional
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methods
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Middle Aged
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Proteinuria
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complications
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urine
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Qi
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Regression Analysis
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Yin-Yang
4.Regulative mechanisms of mammalian target of rapamycin signaling pathway in glomerular hypertrophy in diabetic nephropathy and interventional effects of Chinese herbal medicine.
Jing-Jing YANG ; Yan-ru HUANG ; Yi-gang WAN ; Shan-mei SHEN ; Zhi-min MAO ; Wei WU ; Jian YAO
China Journal of Chinese Materia Medica 2015;40(16):3125-3131
Glomerular hypertrophy is the main pathological characteristic in the early stage of diabetic nephropathy (DN), and its regulatory mechanism is closely related to mammalian target of rapamycin (mTOR) signaling pathway activity. mTOR includes mTOR complex 1 (mTORC1) and mTOR complex 2(mTORC2), in which, the upstream pathway of mTORC1 is phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase(Akt)/adenosine monophosphate activated protein kinase(AMPK), and the representative signaling molecules in the downstream pathway of mTORC1 are 4E-binding proteins(4EBP) and phosphoprotein 70 S6Kinase(p70S6K). Some Chinese herbal extracts could improve cell proliferation via intervening the expressions of the key molecules in the upstream or downstream of PIK/Akt/mTOR signaling pathway in vivo. As for glomerular mesangial cells(MC) and podocyte, mTOR plays an important role in regulating glomerular inherent cells, including adjusting cell cycle, energy metabolism and matrix protein synthesis. Rapamycin, the inhibitor of mTOR, could suppress glomerular inherent cell hypertrophy, cell proliferation, glomerular basement membrane (GBM) thickening and mesangial matrix deposition in model rats with DN. Some Chinese herbal extracts could alleviate glomerular lesions by intervening mTOR signaling pathway activity in renal tissue of DN animal models or in renal inherent cells in vivo and in vitro.
Animals
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Diabetic Nephropathies
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drug therapy
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enzymology
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genetics
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pathology
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Drugs, Chinese Herbal
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administration & dosage
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Humans
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Hypertrophy
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drug therapy
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enzymology
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genetics
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pathology
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Kidney Glomerulus
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drug effects
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metabolism
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pathology
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Signal Transduction
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drug effects
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TOR Serine-Threonine Kinases
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genetics
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metabolism
5.Comparison of Outcomes of Transcatheter and Surgical Procedure in Perimembranous Ventricular Septal Defect Patients with Tricuspid Regurgitation.
Xiao Ke SHANG ; Liang ZHONG ; Rong LU ; Gang Cheng ZHANG ; Mei LIU ; Qun Shan SHEN ; Xin ZHOU ; Chang Yu QIN ; Hong Mei ZHOU
Annals of the Academy of Medicine, Singapore 2016;45(7):322-325
Adolescent
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Adult
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Cardiac Catheterization
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economics
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methods
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Cardiac Surgical Procedures
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economics
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methods
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Cardiac Valve Annuloplasty
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Child
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China
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epidemiology
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Echocardiography
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Female
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Heart Septal Defects, Ventricular
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complications
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diagnostic imaging
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surgery
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Humans
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Length of Stay
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statistics & numerical data
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Male
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Operative Time
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Postoperative Complications
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epidemiology
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Septal Occluder Device
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Tricuspid Valve Insufficiency
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complications
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diagnostic imaging
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surgery
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Young Adult
6.Pharmacokinetics of fudosteine in healthy volunteers.
Li DING ; Jin YANG ; Rong-Shan LI ; Mei ZHOU ; Jian-Ping SHEN ; Yin-Di ZHANG
Acta Pharmaceutica Sinica 2005;40(10):945-949
AIMTo study the pharmacokinetics of fudosteine in healthy volunteers after the single and multiple dose administration.
METHODSThirty-six volunteers were divided into three groups randomly, each group included six men and six women. In the single dose design, the volunteers received either a single dose of 600 mg, 400 mg or 200 mg fudosteine. After a one-week wash out period, the volunteers of 400 mg group participated in the multiple dose design in which each volunteer received 400 mg fudosteine three times a day for five consecutive days. The plasma concentrations were determined by pre-column derivatization HPLC-FL method and the pharmacokinetic parameters of fudosteine were calculated.
RESULTSThe obtained pharmacokinetic parameters of fudosteine in single dose of 600 mg, 400 mg and 200 mg groups were as follows: T1/2 were (2.8 +/- 0.5), (2.7 +/- 0.5) and (3.2 +/- 0.6) h, respectively. T(max) were (0.51 +/- 0.22), (0.59 +/- 0.21) and (0.48 +/- 0.18) h, respectively. C(max) were (16 +/- 4), (11 +/- 3) and (6.1 +/- 1.5) microg x mL(-1), respectively. The AUC(0-10 h) and C(max) correlated linearly with doses, respectively (r > 0.99). The T(max), C(max) and AUC values of fudosteine in healthy male volunteers were smaller than those in female volunteers, and the T1/2 value was longer than that in female volunteers. The obtained multi-dose pharmacokinetic parameters of fudosteine were as follows: C(ss) was (4.1 +/- 0.8) microg x mL(-1); DF was 3.0 +/- 0.7; T1/2 was (2.5 +/- 0.4) h; T(max) was (0.6 +/- 0.3) h; C(max) was (13.2 +/- 1.3) microg x mL(-1).
CONCLUSIONThe values of pharmacokinetic parameters in healthy volunteers were linear in the range from 200 mg to 600 mg. Statistic analysis results showed that the differences of AUC and C(max) between men and women were not resulted from sexual differences, but from the weight differences. There was no significant difference in pharmacokinetic parameters between single dose and multi-dose.
Administration, Oral ; Adult ; Area Under Curve ; Body Weight ; Chromatography, High Pressure Liquid ; methods ; Cystine ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Sex Factors
7.Radiation-induced optic neuropathy in patients with nasopharyngeal carcinoma
Xiao-Lei SHI ; Shan-Shan MA ; Dong-Hua LUO ; Xiao-Ming RONG ; Zi-Chen LI ; Ru-Ying FU ; Qing-Yu SHEN ; Ya-Mei TANG
Chinese Journal of Neuromedicine 2013;12(1):72-75
Objective To investigate the characteristics of radiation-induced optic neuropathy (RON) in patients with nasopharypgeal carcinoma after radiotherapy,and explore its risk factors.Methods A retrospective study was performed on the clinical data of 22 RON patients with nasopharyngeal carcinoma after radiotherapy,admitted to our hospital from January 1997 to January 2011.Their clinical manifestations,eye examinations and cranial MRI data were concluded.Results Visual deterioration,or even,blindness,was the most common manifestation.RON occurred after the initial radiotherapy in 18 cases,and during the initial radiotherapy in 2 cases.And 2 cases developed RON in re-irradiation for recurrences.Blindness developed in 8 eyes,and decreased vision occurred in 27 eyes; 14 patients displayed retinal optic nerve atrophy in the eye examinations.Typical radiological imaging of the skull showed optic nerve enlargement in 30 eyes,optic nerve atrophy in 5 eyes; and the incidence of optic neuropathy was high when radiation dose was over 70 Gy.Conclusion RON may occur in nasopharyngeal carcinoma patients following radiotherapy,having vision disorders,visual field changes,abnormal visual evoked potential and typical cranial imaging performances; the occurrence of RON may be correlated with radiation field and radiation dose; routine eye and imaging examination is of great significance.
8.Transfection and in vitro expression of human microdystrophin gene in rat mesenchymal stem cells.
Shu-hui WANG ; Cheng ZHANG ; Song-lin CHEN ; Mei-juan YU ; Ya-ni ZHANG ; Mei-shan LI ; Fu XIONG ; Yan-chang SHANG ; Shan-wei FENG ; Ben-chang SHEN
Journal of Southern Medical University 2006;26(3):261-265
OBJECTIVETo construct the eukaryotic expression vector of human microdystrophin gene and observe its expression in rat mesenchymal stem cells (rMSCs) in vitro.
METHODSThe plasmid PBSK-MICRO containing human microdystrophin cDNA was digested by restriction endonuclease, and the resultant microdystrophin fragment was inserted into the NotI site of pcDNA3.1(+) to prepare the eukaryotic expression vector-pcDNA3.1(+)/ microdystrophin, which was identified by endonuclease digestion and sequencing. The recombinant plasmid was transfected into rMSCs via lipofectamine, and after G418 selection, the expression of microdystrophin was detected by RT-PCR and indirect immunofluorescence assay.
RESULTSMicrodystrophin gene fragment was correctly inserted into the plasmid pcDNA3.1(+), as conformed by sequencing and digestion with Not I and Hind III. The total mRNA of the transfected rMSCs was extracted and microdystrophin mRNA expression was found in the cells by RT-PCR. Indirect immunofluorescence assay for the protein expression of microdystrophin showed bright red fluorescence in the transfected rMSCs.
CONCLUSIONEukaryotic expression plasmid pcDNA3.1(+)/microdystrophin has been constructed successfully and microdystrophin can be expressed in transfected rMSCs in vitro, which may facilitate further research of Duchenne muscular dystrophy treatment by genetically modified allogeneic stem cell transplantation.
Animals ; Base Sequence ; Cells, Cultured ; Dystrophin ; biosynthesis ; genetics ; Fluorescent Antibody Technique, Indirect ; Gene Expression ; Humans ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Molecular Sequence Data ; Peptide Fragments ; biosynthesis ; genetics ; Plasmids ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection
9.Effects of early nutrition intervention on IGF1, IGFBP3, intestinal development, and catch-up growth of intrauterine growth retardation rats.
Xiao-shan QIU ; Ting-ting HUANG ; Hui-ying DENG ; Zhen-yu SHEN ; Zhi-yong KE ; Kai-yong MEI ; Feng LAI
Chinese Medical Sciences Journal 2004;19(3):189-192
OBJECTIVETo investigate the effects of early nutritional intervention on the serum insulin-like growth factor-1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), intestinal development, and catch-up growth of intrauterine growth retardation (IUGR) rats by giving the IUGR new born rats different protein level diet.
METHODSIUGR rat model was built by starvation of pregnant female rats. Twenty-four IUGR pups and 8 normal pups were divided randomly into 4 groups: normal control group (C group); IUGR control group (S group), IUGR low-protein diet group (SL group), and IUGR high-protein diet group (SH group). Detected the serum IGF1, IGFBP3, body weight, body length, intestinal weight length, intestinal villi height (VH), crypt depth (CD), villi absorbing area (VSA), mucous thickness (MT), and disaccharidase at the 4th week.
RESULTS(1) The SH group showed the fastest catch-up growth, serum IGF1, IGFBP3, VH, and VSA were significantly higher than those of normal control group and IUGR control group. The intestinal weight and length, and the activities of lactase and saccharase of the SH group also reached the normal control group level. (2) The SL group kept on small size, the serum IGF1, IGFBP3, and most of intestinal histological indexes were all significantly lower than other groups. (3) IGF1, IGFBP3 were positively correlated to intestinal VH, VSA, saccharase, body weight and length.
CONCLUSIONSThe serum IGF1 was a sensitive index to the catch-up growth. The early nutritional intervention of high-protein diet after birth is helpful for the catch-up growth of IUGR through promoting the intestinal development and the absorption of nutrition.
Animals ; Animals, Newborn ; growth & development ; Body Weight ; drug effects ; Dietary Proteins ; pharmacology ; Female ; Fetal Growth Retardation ; blood ; etiology ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; metabolism ; Intestines ; growth & development ; pathology ; Nutritional Physiological Phenomena ; Pregnancy ; Random Allocation ; Rats ; Rats, Sprague-Dawley
10.Effect of different early nutritional interventions on catch-up growth of rats with intrauterine growth retardation.
Xiao-shan QIU ; Ting-ting HUANG ; Zhen-yu SHEN ; Hui-ying DENG ; Zhi-yong KE ; Kai-yong MEI ; Feng LAI
Chinese Journal of Pediatrics 2004;42(10):782-786
OBJECTIVEAbout 20 - 50% individuals with intrauterine growth retardation (IUGR) could not achieve catch-up growth and remain small in size till adulthood. There are few reports on the relation between intestinal development and body catch-up growth of IUGR. Studies showed that early "nutritional programming" would results in long-term effects on the body growth and organic function, and gastrointestinal development is closely related to the body development as well. The authors aimed to study the effect of early nutritional interventions on serum IGF1, IGFBP3, intestinal development and catch-up growth of pups with IUGR by using diets with different protein and caloric levels during the first four weeks of life.
METHODSAn IUGR rat model was established by maternal nutrition restriction during pregnancy. Thirty-two IUGR female pups were divided randomly into 4 groups (8 pups in each group) and eight normal female pups as control. The groups and interventions were (1) Normal control group (C group); (2) IUGR control group (S group), (3) IUGR low-protein diet group (SL group); (4) IUGR high-protein diet group (SH group); (5) IUGR high-caloric group (SA group). The serum IGF1, IGFBP3, body weight, body length, and intestinal weight, length, intestinal villi height (VH), crypt depth (CD), villi absorbing area (VSA), mucous thickness (MT) were measured at the 4(th) week of life.
RESULTS(1) At the 4(th) week, the serum IGF1 (724.0 +/- 153.5 ng/ml), IGFBP3 (9.69 +/- 3.13 ng/ml), and VH (416.9 +/- 46.3 microm), VSA (115.9 +/- 24.0 x 10(3) microm(2)), MT (583.9 +/- 68.5 microm) in the SH group were significantly higher than those of normal control group (539.4 +/- 198.4 ng/ml, 4.77 +/- 2.98 ng/ml and 322.1 +/- 25.8 microm, 85.8 +/- 17.8 x 10(3) microm(2), 480.0 +/- 61.5 microm) and IUGR control group (P < 0.05). The intestinal weight (1.91 +/- 0.16 g) and length (80.67 +/- 9.47 cm) in the SH group was not significantly different from the normal control group (2.24 +/- 0.22 g and 74.77 +/- 9.06 cm, P > 0.05). The SH group showed the fastest catch-up growth. Their body weights (40.14 +/- 11.03 g) at the 3(rd) week and body lengths (23.61 +/- 0.49 cm) at the 4(th) week of life reached the normal ranges of the control group (44.65 +/- 5.36 g and 23.10 +/- 1.42 cm, P > 0.05). (2) The serum IGF1 (346.7 +/- 85.3 ng/ml), IGFBP3 (1.4 +/- 0.21 ng/ml), body weight (21.41 +/- 3.54 g) and body length (15.96 +/- 1.29 cm) and the most of intestinal indexes in the SL group were markedly lower than other groups at the 4(th) week of life (P < 0.05).
CONCLUSIONThe serum IGF1 was a sensitive marker to reflect the catch-up growth and nutritional status, and IGF1 was positively correlated with the intestinal development and body growth. When given different nutritional interventions during the first four weeks of life, high protein diet is more helpful for the IUGR catch-up growth by promoting the intestinal development and the absorption of nutrition.
Animal Nutritional Physiological Phenomena ; Animals ; Animals, Newborn ; growth & development ; Dietary Proteins ; administration & dosage ; Disease Models, Animal ; Female ; Fetal Growth Retardation ; blood ; diet therapy ; Insulin-Like Growth Factor I ; analysis ; Pregnancy ; Prenatal Nutritional Physiological Phenomena ; Rats