Objective To investigate the protective effects of recombinant human insulin-like growth factor-1 ( rhIGF-1) on apoptosis of diaphragm in rats with COPD and its impact on pulmonary function. Methods Forty-five male Wistar rats were randomly divided into three groups, ie. a normal control group, a model group, and an IGF-1 intervention group, with 15 rats in each group. The rats in the model group and IGF-1 group were exposed to 5% smoke ( 30 min perday, lasting 28 days) in a sealed box, and 200 μg lipopolysaccharide was injected intratracheally on the 1st and 14th day. The rats in the IGF-1 group were given rhIGF-1 ( 60 μg /100 g) additionally by subcutaneous injection once a day, lasting 28 days. On the 1st, 14th, 28th day, 5 rats from each group were sacrificed. The weight, rate of apoptosis, Fas gene and Fas protein expression of isolated diaphragms were detected. The pulmonary function was measured on the 28th day before sacrificed. Results The mass of diaphragms, minute ventilation ( VE) , peak expiratory flow ( PEF) , inspiratory capacity ( IC) , forced expiratory volume in 0. 3 second ( FEV0. 3) of themodel groupand IGF-1 group were all decreased compared with the control group ( P lt; 0. 05) . The mass of diaphragms, VE, IC of the IGF-1 group were higher than those of the model group ( P lt;0. 05) , and the differences of PEF and FEV0. 3 were not significant ( P gt; 0. 05) . On the 14th, 28th day, rate of apoptosis, Fas gene and protein expressions in the IGF-1 group were lower than those in the model group, and still higher than those in the control group ( P lt; 0. 05) . Conclusions Fas/FasL mediated apoptosis way is involved in the diaphragm apoptosis. rhIGF-1 may reduce the apoptosis of the diaphragmand improve the VE and IC of rats with COPD by intervening Fas/FasL pathway.
Objective To investigate the mechanismof lung injury caused by paraquat poisoning by observing the changes of fibrogenic cytokines in acute paraquat poisoned rats and the effects of pyrrolidine dithiocarbamate ( PDTC) . Methods Sprague-Dawley rats were randomly divided into three groups, ie. acontrol group ( n =6) , a PDTC group ( n =36) , a paraquat group ( n = 36) , and a paraquat + PDTC group( n =36) . The rats in the PDTC group, the paraquat group, and the paraquat + PDTC group were subdivided into 6 subgroups sacrificed respectively on 1st, 3rd,7th,14th, 28th and 56th day after the treatment. The levels of transforming growth factor-β1( TGF-β1 ) , platelet-derived growth factor ( PDGF) , insulin-like growthfactor-1 ( IGF-1) in serum were measured. Meanwhile the expression of connective tissue growth factor ( CTGF) and hydroxyproline in lung tissues were detected. The relationship of above cytokines with hydroxyproline was analyzed. Results The destructive phase in early ( 1 ～7 d) was characterized by hemorrhage, alveolar edema, and inflammatory cell infiltration. The proliferous phase in later stage ( 14 ～56 d) was characterized by diffused alveolar collapse with fibroblast proliferation and patchy distribution of collagen fibers. Compared with the control group, the level of TGF-β1 on all time points, the level of PDGF from7th to 56th day, the level of IGF-1 from3rd to 56th day in the paraquat group all significantly increased ( P lt;0. 01) . Immunohistochemistry results showed CTGF positive cells mainly located in aleolar epithelialcells, endothelial cells,macrophages in early stage, and fibroblasts were main positive cells on the 28th and the 56th day. The expression of CTGF in the paraquat group increased gradually compared with the control group on different time points ( P lt; 0. 05 or P lt; 0. 01) . Meanwhile, the levels of above cytokines were positively correlated with the level of hydroxyproline. Noteworthy, PDTC treatment led to significant decreases of above cytokines compared with the paraquat group in corresponding time points ( P lt;0. 05 or P lt;0. 01) .Conclusions Over expressions of IGF-1, TGF-β1 , PDGF, IGF-1 and CTGF may play important roles in lung fibrosis of paraquat poisoned rats. PDTC, as a b NF-κB inhibitor, may inhibits NF-κB activity and further significantly decreases expressions of cytokines, leading to significantly attenuated pulmonary inflammation and fibrosis. However, the mechanisms of PDTC intervention still remain to be explored.
OBJECTIVE: To investigate the effect of electroacupuncture on mRNA expression of NGF and IGF-1 in injured nerve. METHODS: Sciatic nerve injury model was established by transection of right side sciatic nerve in 90 male SD rats, which were randomly divided into two groups. The experimental group was treated with electroacupuncture, no treatment in the control group. The distal part of the injured nerve was harvested after 1, 2, 4, 6 and 10 weeks of operation and stored in the liquid nitrogen. The total RNA was extracted by the TRIzol reagent. Reverse transcriptase-polymerase chain reaction(RT-PCR) was used to detected the mRNA expression of NGF and IGF-1. RESULTS: The mRNA expression of NGF in the experimental group was increased quickly from the second week, and reached to highest level in the fourth week. It was much higher than that of the control group (P lt; 0.05). Then it began to decline in following time and approximately reached to the level of the first week after 10 weeks of operation. The mRNA expression of IGF-1 in the experimental group was remarkably increased in the second and fourth week, and which was much higher than that of the control group respectively(P lt; 0.05). Although the mRNA expression of IGF-1 after 10 weeks of operation in the experimental group was higher than that of the control group, but there was no significant difference between the two groups(P gt; 0.05). There was linear correlation in the fourth week between mRNA expression of NGF and IGF-1 in the experimental group. CONCLUSION: The mRNA expression of NGF and IGF-1 can be elevated in injured nerve at early stage interfered with electroacupuncture.
For the purpose of understanding the distribution of insulin-like growth factor-1 (IGF-1) receptor on the tendon cell, the continuous cultured tendon cell line was studied by following experiments. With the methods of immunohistochemical study and flow cytometric study, the density of IGF-1 receptor of the primary, 6th and 13th generation of tendon cell was analyzed. The results showed that there was no difference of the receptor density among those generations. However, in the cell cycle, the numbers of IGF-1 receptor in G2M phase tendon cells were more than that in G1 phase cells (P lt; 0.01). These works provided sufficient evident which suggested there were stable density of IGF-1 receptor on the tendon cell though out the life span of tendon cell. This may build some foundation in growth control of tendon cell by growth factor in the research of tendon tissue engineering.
The purpose of this study was to find some solutions to the problem of tendon cell proliferation control. Under the condition of in vitro culture, several materials including IGF-1 receptor antibody and mRNA antisense oligonucleotide were added to the culture medium to block the IGF-1-Receptor system. The effect of the material on the tendon cell proliferation was judged by cell count after incubation of 48 hours. The results showed that both IGF-1 Receptor antibody (IGF-1R alpha) and IGF-1 Receptor mRNA antisense oligonucleotide had negative effect on tendon cell proliferation (P lt; 0.01 and P lt; 0.05). These findings lead us to think that the above two materials could be used in the experiment of tendon adhesion preventing and living ready-made tendon producing.
ObjectiveTo evaluate the possible role of the expression of insulin-like growth factor-1 receptor (IGF-1R) in determining rectal cancer radiosensitivity. MethodsThe paired preradiation biopsy specimens and postoperative specimens were obtained from 87 patients with rectal cancer in the department of digestive tumor surgery, Jiangsu Province Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from January 2009 to December 2010. The IGF-1R expression was examined by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR). The tumor radiosensitivity was defined according to Rectal Cancer Regression Grade, then the relation between the IGF-1R expression and tumor radiosensitivity was evaluated. ResultsCompared with the preradiation biopsy specimens, IGF-1R expression significantly increased in the paired postoperative specimens of the residual cancer cells (Plt;0.001). The IHC result demonstrated IGF-1R overexpression was significantly associated with a poor response to radiotherapy (rs=0.401, Plt;0.001); RT-PCR detection of IGF-1R expression on preradiation biopsy specimens also showed that IGF-1R mRNA negative patients had a higher radiation sensitivity (rs=0.497, Plt;0.001). ConclusionDetection of IGF-1R expression may predict radiosensitivity of preoperative irradiation for rectal cancer.
Objective To investigate the impacts of neoadjuvant chemotherapy on the expression of insulin-like growth factor-1 receptor (IGF-1R) and on operation procedure and the significance of prognosis. Methods The expression of IGF-1R in 40 patients with breast cancer before and after neoadjuvant chemotherapy was measured by immunohistochemistry. The diagnosis was proved by core biopsy. All the patients took the TAC chemotherapy regimen. Modified radical operation was performed after two chemotherapy cycles and the IGF-1R expression was measured again. The clinical effect of neoadjuvant chemotherapy was assessed according to WHO criterion by measuring the size of tumor by physical examination and B type ultrasound. Results After neoadjuvant chemotherapy the tumor size shrank in 29 patients, there was no CR (complete response) or PD (progressed disease) to be documented. IGF-1R expression could be downregulated in 25 patients. Conclusion Neoadjuvant chemotherapy can inhibit the tumor growth by downregulation of the expression of IGF-1R.
Objective To determine the effect of insulin-like growth factor-1 (IGF-1) on angiogenesis in mouse breast cancer model of lower and normal serum IGF-1 levels after using angiogenesis inhibitor ginsenoside Rg3 （GS Rg3）. Methods The breast cancer models were established in control mice and liver specific IGF-1 deficient (LID) mice by feeding DMBA and were treated with GS Rg3. Vascular endothelial growth factor (VEGF) and F8-RAg were detected by immunohistochemical method in breast cancer tissues. IGF-1 gene and angiogenesis relating genes were detected by gene chip in breast cancer and normal breast tissue. Results The incidence rate of breast cancer in LID mice was lower than that in control mice (P＜0.05). VEGF expression and microvessel density of LID mice were lower than those in control mice (P＜0.05). Compared to the control mice, IGF-1, FGF-1, TGF-β1 and HGF genes were increased, and FGFR-2, PDGF-A and PDGF-B genes were decreased in breast cancer of LID mice. After GS Rg3 treatment, VEGFa, EGF, EGFR, PDGF-A and FGFR-2 genes were increased, IGF-1 and TGF-β1 genes were decreased in breast cancer of LID mice compared with the control mice. Conclusion IGF-1 may be involved in mouse breast cancer progression and associated with the growth of blood vessels. Angiogenesis inhibitor may play an antitumor role by IGF-1 and TGF-β1.
【Abstract】Objective To study the changes of insulin-like growth factor-1(IGF-1) in serum of patients with obstructive jaundice.Methods The clinical data of 20 patients with obstructive jaundice were collected and the measurement of serum TNFα,ALT, ALP, endotoxin and IGF-1 were performed. Results The serum IGF-1 in obstructive jaundice was significantly lower than that in gallbladder stone(P＜0.01), while endotoxin, TNF-α, ALT，ALP and TB were higher(P＜0.01). After the biliary duct obstruction was removed, the serum IGF1 in obstructive jaundice was significantly higher than that before operation and serum endotoxin， TNF-α, ALT， ALP and TB were significantly lower than that before operation(P＜0.01). A significant negative correlation was found between serum IGF-1 and serum endotoxin in benign obstructive jaundice(r=-0.761, P＜0.01). ConclusionIn obstructive jaundice, endotoxemia can affect the secretion of IGF-1 from liver. IGF-1 can be used as an index to judge the liver function in obstructive jaundice.