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1.
AIM: To study the role of high level of endogenous nitric oxide (NO) in apoptosis of alveolar epithelial cells in the development of pulmonary fibrosis in rats. METHODS: The content of nitrite/nitrate (NO2-/NO3-) in out-flowing pulmonary blood (OPB) was assayed by nitric acid reduction method. The apoptosis of alveolar epithelial cells was observed by TdT-mediated dUTP nick-end labeling (TUNEL) and electron microscopy, respectively. The above indices were observed on the day 14 and the day 30 after intratracheal administration of BLMA5 alone or along with blockade of iNOS by aminoguanidine (AG) in rats. RESULTS: (1) Both the content of NO2-/NO3- in OPB and the number of apoptotic alveolar epithelial cells in lung were increased in BLMA5 14 d group, compared with normal control group and BLMA5 30 d group, respectively (P<0.05). The high level of NO2-/NO3- in OPB and the apoptosis of alveolar epithelial cells were ameliorated by AG. CONCLUSION: The apoptosis of alveolar epithelial cell is induced by high level of endogenous NO in the development of pulmonary fibrosis.  相似文献   

2.
AIM: To observe the kinetic alteration of nitric oxide formation in the lungs in the development of pulmonary fibrosis in the rat. METHODS: The contents of hydroxyproline in the lungs, NO2-/NO3- (nitrite/nitrate) in out-flowing and in-flowing pulmonary blood (OPB, IPB) were assayed on the day 7, 14, 21, 30 and 70 after intratracheal administration of bleomycin A5 . The content of NO2-/NO3- in supernatants of culture of the alveolar macrophages (AMs) and the amount of iNOS positive stain cells in lung tissue section were also observed in the rat on 14th day after-bleomycin A5 administration. RESULTS: The content of lung hydroxyproline had no change on the 7th day, increased on the 14th day (P<0.05), increased significantly on the 21th day, 30th day and 70th day post-bleomycin A5 compared with control rats. On the 7th day and 14th day, the content of NO- 2 /NO3- increased in OPB and decreased in IPB (P<0.01). On the 21th day, the content of NO2-/NO3- abated in OPB (P>0.05) but still decreased in IPB (P<0.01). On the 30th day and the 70th day, the NO2-/NO3- level recovered both in OPB and IPB. AMs from rats on the 14th day post-bleomycin A5 showed significant elevation (P<0.01) in NO2-/NO3- level. The amount of iNOS positive stain cells increased in rats on the 14th day post-bleomycin A5. CONCLUSION: The amount of NO in the lungs was high in the initial phase of fibroproliferative reaction induced by bleomycin A5 ,and these might be associated with the enhanced ability of AMs to release NO and the increased amount of iNOS.  相似文献   

3.
AIM: To observe the changes in proliferation and apoptosis of macrophages in the development of pulmonary fibrosis in rats. METHODS: The number of macrophages, apoptotic cells, the proliferation index (PI) and MTT activity of macrophages were assayed on the day 14 and the day 30 after intratracheal adminstration BLMA5 in rats. RESULTS: (1) The number of alveolar macrophages was increased in BLMA5 14 d group and in BLMA5 30 d group, compared with sham 14 d group and sham 30 d group, respectively. The number of macrophages in BLMA5 14 d group was higher than that in BLMA5 30 d group. (2) The PI of macrophages increased in BLMA5 14 d group, and decreased in BLMA5 30 d group. (3) The number of apoptotic cells increased both in BLMA5 14 d group and BLMA5 30 d group. The number of apoptotic cells in BLMA5 14 d group was lower than that in BLMA5 30 d group. (4) The MTT activity of macrophages was higher in BLMA5 14 d group and in BLMA5 30 d group than that in sham 14 d group and sham 30 d group, respectively. CONCLUSIONS: The ability of proliferation increased at first, and then decreased, but the apoptosis of macrophages increased all the time, in the development of pulmonary fibrosis. This might be partly contributed to the changes of the number and function of macrophages in lung.  相似文献   

4.
AIM: To observe free radicals (MDA, NO) and iNOS of patients with severe acute respiratory syndrome (SARS) and to explore its significance. METHODS: MDA, NO2-/NO3- and iNOS were determined in SARS patients during the early, recovery and follow-up stage, front doctors and nurses (contact group) and health people (health control). RESULTS: The level of MDA during first stage was higher than that of recovery stage and the MDA level of recovery stage was higher than that of follow-up stage, contact group, and health control group (P<0.01). The content of NO2-/NO3- during early stage was higher than that of other groups, and the NO2-/NO3- contents of recovery stage, follow-up stage were higher than that of contact group and health control group (P<0.01), respectively. The mean of iNOS during early stage was highest than that of other stages (P<0.01) and the mean of recovery stage was higher than that of contact group (P<0.05), there were no difference in iNOS activity among any other groups (P>0.05). CONCLUSION: The pathological injury in pathogenesis of SARS is related to free radicals.  相似文献   

5.
AIM:To observe the changes of iNOS and eNOS in lung tissue and NO in bronchoalveolar lavage fluid (BALF) in smoking rats.METHODS:80 Wistar rats were divided into control, smoking group, L-NIL group and L-NAME group (rats were exposed to smoke and injected (i.p.) with selective iNOS inhibitor L-NIL or NOS inhibitor L-NAME). iNOS and eNOS protein levels in whole lung were detected by immunohistochemical staining, and NOS mRNA was quantified using RT-PCR. In addition, NO2-/NO3- was determined using Griess assay.RESULTS:The expression of iNOS mRNA and protein in smoking rats increased, the expression of eNOS mRNA and eNOS protein decreased, and the total cell count and the level of NO2-/NO3-in BALF increased(P<0.05). In vivo, L-NIL reduced the total cell count and NO2-/NO3- in BALF (P<0.05), while L-NAME had no effect on them.CONCLUSION:Cigarette smoke increased expression of iNOS mRNA and protein and decreased expression of eNOS mRNA and protein. The large amount of NO generated by iNOS may amplify inflammation in lung tissue.  相似文献   

6.
AIM: To approach the changes of ET and NO levels of mice bearing sarcoma 180 (S180 ) during different period(5、10 and 15 days) and the relationship between ET、NO and tumor’s development METHODS: Adopting mice bearing S180 as the models, the levels of ET and NO2-/NO3- in serum were detected, and the weight of isolated tumors was measured On the basis of the regulation of these changes, their relationships were explored RESULTS: The levels of ET and NO2-/NO3- of mice bearing S180 were higher than that of the control group (not bearing tumor) ( P< 0.05) Along with the development of the tumors, the levels of NO2-/NO3-and tumors weight both increased ( P< 0 05) ET also had an increasing tendency There was a positive correlation between the level of NO2-/NO3- and tumor weight ( r =0.995, P< 0.05) Ratio value of (NO2-/NO3-)/ET decreased at first and then increased CONCLUSION: ET and NO have links with the development of S180 There may be cooperation between ET and NO during the development of tumor.  相似文献   

7.
AIM: To investigate the changes in nNOS and iNOS expression of hippocampal CA3 pyramidal neurons and NO2-/NO3- level of hippocampal homogenate of rats induced by stress, and to explore the effect of phenytoin on them. METHODS: Rats were subjected to forced-swimming stress, phenytoin was administered(ip) at 30 min before stress. Using the immunohistochemistry and the computerized image technique, the expression levels of nNOS and iNOS of rat hippocampal CA3 pyramidal neurons were assayed quantitatively, and the NO2-/NO3- level of hippocampal homogenate was also measured using nitric acid deoxidize enzyme method. RESULTS: The nNOS average grey degree of hippocampal CA3 pyramidal neurons was significantly lower in stress group (155.42±3.77)than that in control group(164.54±4.62)and in stress plus phenytoin group(164.27±2.55)(P<0.01); The iNOS relative sectional area proportion of hippocampal CA3 pyramidal neuron was significantly larger in stress group(5.87%±2.90%) than that in control group (0.90%±0.89%) and in strers plus phenytoin groups (0.90%±0.88%)(P<0.01); The NO2-/NO3- level of hippocampal homogenate was significantly higher in stress group(42.75 umol/L±14.49 umol/L)than that in control group(21.23 umol/L±6.99 umol/L)and in stress plus phenytoin group(18.40 umol/L±8.11 umol/L)(P<0.01). CONCLUSION: It is suggested that the stress could induce nNOS and iNOS expression in CA3 pyramidal neurons and excessive production of NO in hippocampus of rats, which could be inhibited by phenytoin.  相似文献   

8.
AIM:To explore the effects of levcromakalim(Lev) on pulmonary arterial endothelial cells (PAEC) and smooth muscle cells (PASMC) exposed to hypoxia and the mechanisms involved.METHODS:The effects of Lev on [Ca2+]i, and expression of PKCα, eNOS, iNOS and PDGF-B mRNA and protein levels were observed. The nitrite (NO2-) and entothelin-1(ET-1) concentrations in supernatant in cultured PAEC and PASMC were measured. The proliferation and apoptosis of PASMC was also detected.RESULTS:When PASMC were exposed to hypoxia, Lev reduced concentration of ET-1 in cultured cell supernatant, lowed the expression of PKCα, iNOS and PDGF-B both at mRNA and protein levels, decreased [Ca2+]i concentration, increased proliferation and promoted the apoptosis in PASMC. However, in the presence of Lev, the [Ca2+]i concentration was not changed in the hypoxic PAEC. The NO2- concentration in cultured cell supernant and expression of eNOS at mRNA and protein levels in hypoxic PASMC and PAEC were also unchanged. The downregulated ET-1 activity in PASMC and PAEC and proliferation in PASMC involved in the inhibition of PKCα signaling pathway.CONCLUSIONS:Lev reduce some disadvatage effect of hypoxia on PASMC and PAEC. The mechanism of Lev action may partly involve in the downregulation of PKCα signaling functions.  相似文献   

9.
AIM: To investigate the preventive effect of PNS on chronic hypoxic pulmonary hypertension in rats. METHODS: Pulmonary arterial pressure observation, hematocrit (Hct)measurement, biochemical analysis and transmission electron microscopy were conducted to investigate the role of PNS. RESULTS: (1)Mean pulmonary arterial pressure (mPAP), right ventricular mean pressure (RVMP) and Hct were significantly higher in hypoxia group (H group) than that of control group (C group) and were much lower in hypoxia with PNS group (HT group) than that in H group; (2) Nitric oxide (NO2-/NO3-) concentration and nitric oxide synthase (NOS) activity in the plasma and the lung tissue, total superoxide dismutase (T-SOD) and copper/zinc-containing enzyme (Cu/ZnSOD) activities in the plasma were all significantly lower in H group than that in C group and were much higher in HT group than that in H group, but NO2-/NO3- concentration and NOS activity were still markedly decreased in comparison with C group; (3) Injury of endothelial cells in pulmonary arteriole was improved obviously in HT group Compared with H group. CONCLUSIONS: These results suggest that PNSreduces the increase in mPAP, probably through adjusting NOlevel, anti-damaging effectof free radicals, inhibiting the injury of endothelial cells and decreasing Hct.  相似文献   

10.
AIM:To study the effect of human complement C5b~9 complex on nitric oxide(NO) synthesis of glomerular mesangial cells (MC). METHODS: First, the human complement C5b~9 complexes were isolated and glomerular MC of rats were cultured. Second, the MC were stimulated with C5b~9 complex and changes of metabolism products of NO(NO3- and NO2) in MC culture supernatant at 6,24 and 48 hours after C+5b~9 stimulating were detected. Moreover, cGMP levels in cultured MC were also measured. RESULTS: NO3-/NO2- contents from culture supernatant and cGMP levels in MC were increased parallelly after C5b~9 complex stimulation. Further, NO synthesis was inhibited by L-NG-nitro-arginine-methylester(L-NAME). CONCLUSION: NO synthesis of rat glomerular MC was incerased by human complement C5b~9 stimulation.  相似文献   

11.
AIM:To observe the changes in nitric oxide(NO) and peroxynitrite anion (ONOO- ) in the injuried lung following the ischemia-reperfusion of hind limbs and evaluate the contribution of NO and ONOO- to tissue injury.METHODS:A model of hind limbs ischemia was made by clamping infrarenal aorta with a microvascular clip and lung injury occurring after reperfusion.Lung t issue was obtained from the animals received sham operation(group 1),4 hours ischemia without reperfusion(group2),1 hour reperfusion following 4 hours ischemia(group3)and 4 hours reperfusion fol owing 4 hours ischemia(group4).The contents of MDA,NO2-/NO3- and the activities of SOD in the lung were examined.Immunohistochemical echnique was used to determine the immunoreactivity to iNOS and nitrotyrosine(NT)-a specific "footprint" of peroxynitrite.RESULTS:Compared with group1 and group2,the contents of MDA and NO2-/NO3- increased significantly (P<0.05) and the activities of SOD decreased markedly(P<0.05) in group3 and group4.Immunohistochemical examination demonstrated intense staining for iNOS and NT throughout the lung in group3 and group4.CONCLUSION:NO and ONOO- are involved in oxidant-mediated lung injury following reperfusion of ischemic hind limbs.  相似文献   

12.
AIM: To study the effects of nitric oxide (NO) on mitochondrial damage caused by exogenous calcium. METHODS: Normal myocardial mitochondria were divided into three groups; L-arginine control group (CG), Ca2+-damaged group (DG) and L-NAME-preserved group (PG). Mitochondria of all groups were incubated at 30 ℃ with reaction medium containing 20 μmol/L EDTA, 100 μmol/L CaCl2 and 1 μmol/L L-NAME with 100 μmol/L CaCl2 respectively. Then the NO2-/NO3- contents, mitochondrial viability and membrane potential were investigated. RESULTS: The NO2-/NO3- contents of DG was obviously higher than that of CG and PG, meanwhile, there was no obvious difference between CG and PG. Mitochondrial viability and membrane potential of DG were significantly lower than that of CG and PG, and negatively related to NO-2/NO-3 contents (r=-0.5297, P<0.01; r=-0.6041, P<0.01). But, the mitochondrial viability and membrane potential of PG were still lower than that of CG. CONCLUSION: Exogenous calcium could activate mitochondrial nitric oxide synthase resulting in NO production and the latter play an important role in decreasing mitochondrial viability and membrane potential.  相似文献   

13.
AIM:To study the protective effect of Ligustrazini(LGT) on gut barrier function after hemorrhagic shock-reperfusion. METHODS: Thirty white rabbits were divided randomly into 3 groups: control group (A),shock group (B) and LGT group (C). Malondialdehyde(MDA), tumor necrosis factor-α(TNFα), interleukin-1β(IL-1β) and nitric oxide products(NO2-/NO3-) contents were measured in intestinal mucosa at 3 hours following reperfusion,culture of bacteria in blood from rabbits of 3 groups was carried out,the intestinal mucosa was examined under optical and electron microscope. RESULTS: MDA, TNFα, IL-1β and NO2-/NO3- contents of intestinal mucosa remained unchanged in group C,but increased significantly in group B, compared with group A. Incidence of bacterial translocation in group B was markedly higher than that in group A at 30 min following reperfusion,there was not any difference between group A and group C. Under light and electronic microscope,in comparison with A and C groups,intestinal mucosa damage in B group became more severe. CONCLUSION: LGT can protect gut barrier from intestinal ischemia-reperfusion injury induced by hemorrhagic shock through reducing oxygen free radicals,raising nitric oxide and preventing inflammation.  相似文献   

14.
AIM: To investigate the relationship between the level of interleukin-2 (IL-2), tumour necrosis factor-α (TNF-α) and nitric oxide (NO) in aqueous humor after intraocular lens implantation. METHODS: New Zealand rabbits were divided randomly into three groups: (1) control group; (2) extracapsular cataract extraction group (ECCE); (3) extracapsular cataract extraction and posterior chamber intraocular lens implantation group (ECCE+IOL). The inflammation in all experimental rabbit eyes was observed via zoom-photo slit-lamp microscope on 1, 3, 7, 14 d and 30 d postoperation. Meanwhile, aqueous humor was drawn for white blood cell (WBC) counting and classifying and for determining IL-2, TNF-α and NO2-/NO3- contents. RESULTS: (1) The level of IL-2 and TNF-α and NO2-/ NO3- in aqueous humor of ECCE+IOL group were higher than that in ECCE and control at 1 to 14 days postoperation, respectively, it increased to peak value at 3 to 7 days postoperation and decreased gradually two weeks postoperation; (2) The changes in IL-2, TNF-α and NO2-/NO3- in each group were basically similer; (3) The changes of IL-2 and TNF-α level were closely related with NO content in aqueous humor (r=0.69, P<0.01 and r=0.98, P<0.01). CONCLUSION: IL-2, TNF-α and NO play an important role in intraocular inflammation intraocular lens implantation.  相似文献   

15.
AIM:To investigate the effect of Se-containing spirulina phycocyanin (Se-SPC) on liver injury of mice induced by carbon tetrachloride (CCl4). METHODS:The mouse model was conducted by intragastric feeding with 2% CCl4 oil for three times, meanwhile Se-SPC, spirulina phycocyanin (SPC) and Na2SeO3 were injected (ip) to various groups for 7 days. Then selenium (Se), glutathione peroxidase (GPx), superoxide dismutase (SOD), alanine aminotransferase (ALT), malondiaoldehyde (MDA) and nitric oxide (NO) levels in blood and liver were measured. RESULTS:The level of Se,GPx and SOD activities were obviously higher(P<0.05)but ALT activity,MDA and NO2-/NO3- levels were remarkably lower(P<0.05)in Se-SPC treated groups than those in CCl4 groups,and effects of high dose Se-SPC on Se,GPx,MDA and NO2-/NO3- were even more significant(P<0.01).Under the same dose of Se or protein,effects of all selected targets in Se-SPC groups were more efficient than those in SPC groups and inorganic-Se groups.Furthermore,Se levels had a positive correlation with GPx activity(r=01705),which had negative correlation with levels of MDA,NO2-/NO3- and ALT(r=-0.629,r=-0.336,r=-0.457,respectively), and positive correlations between ALT activity and MDA or NO2-/NO3- level were found (r=0.519,r=0.641). CONCLUSION:These results indicated that Se-SPC may attenuate liver injury of mice induced by CCl4 through its anti-inflammatory action and enhancing selenoenzyme expression.  相似文献   

16.
AIM:To study the effect of fructose-1, 6-diphosphate (FDP) on adriamycin(ADM)-induced cardiomyocyte apoptosis in rats. METHODS:Twenty-four Wistar rats were randomly divided into three groups: control group, ADM treated group and FDP intervention group. The contents of malondialdehyde (MDA) and NO2-/NO3-, the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were determined by colorimetric method in myocardial tissue, and the cardiomyocyte apoptosis was detected by TUNEL method in myocardial tissue, and the expression of inducible nitric oxide synthase (iNOS) mRNA, Bcl-2 mRNA and Bax mRNA in myocardial tissue were detected by in situ hybridization. RESULTS:The contents of NO2-/NO3- and MDA in myocardial tissue, the expressive levels of iNOS mRNA and Bax mRNA in cardiomyocyes and its apoptotic amounts in FDP intervention group were significantly lower than those in ADM treated group (P<0.01). However, the activities of SOD and GPx in myocardial tissue, the expressive level of Bcl-2 mRNA of cardiomyocytes in FDP intervention group were significantly higher than those in ADM treated group (P<0.01). CONCLUSION:FDP antagonized the reduced expression of Bcl-2 mRNA and increased expression of Bax mRNA in myocardial tissue induced by ADM, and in turn inhibited ADM-induced cardiomyocyte apoptosis.  相似文献   

17.
AIM: To investigate the effects of nitric oxide (NO) and NO synthase (NOS) inhibitor NG-nitro-L arginine (L-NA) on LPS induced-lung injury in rats. METHODS: Forty healthy male SD rats, weighing 300±20 g, were used. The animals were anesthetized with 20% urethane 1 g·kg-1. Common carotid artery (CAA) and jugular vein were exposed through a median incision in the neck. Mean arterial pressure (MAP) was measured through a pressure transducer connected with intubation of CAA. The animals were randomly divided into five groups: group 1: control; group 2: LPS (5 mg·kg-1, iv); group 3: high dose L-NA (20 mg·kg-1 intraperitoneal injection, ip); gropu 4: middle dose L-NA (10 mg·kg-1, ip); group 5: low dose L-NA (5 mg·kg-1, ip). Group1 : 0.9% saline solution was given and the animals were killed 6 h after the saline solution. Gruop 2: saline solution was given 3 h after LPS and the animals were killed 3 h after administration. Group 3, 4 and 5: L-NA was given 3 h after LPS iv and the animals were killed 3 h after administration, respectively. The pulmonary was removed immediately. The pulmonary coefficient and water content in pulmonary tissue were calculated (%). The NO2-/NO3- content in plasma, MDA content and NOS, SOD activity in the pulmonary tissue were measured. RESULTS: L-NA significantly decreased pulmonary coefficient and water content in pulmonary tissue and ameliorated LPS induced lung injury. The effect in high dose group was better than that in low dose group. L-NA significantly decreased NO2-/NO3- content in plasm, decreased MDA content and inhibited NOS activity and enhanced SOD activity in the pulmonary tissue. CONCLUSION: It may be concluded that L-NA has a beneficial effect on lung injury induced by LPS.  相似文献   

18.
AIM: To explore the effect of antiserum against rat complement C5b-9 complexes on nitric oxide synthesis and pathologic changes in renal tissue of rats with mesangioproliferative glomerulonephritis. METHEDS: The rat model of mesangioproliferative glomerulonephritis,namely,anti-thymocyte serum nephritis(ATSN) was established and the rats with ATSN were treated with antiserum against complement C5b-9 complexes. Some parameters related to NO and pathologic changes of the rats were observed.RESULTS: Anti-C5b-9 serum not only reduced the expression of inducible NO synthase(iNOS) mRNA in renal tissue and urinary content of nitrate/nitrite(NO3-/ NO2-) of rats with ATSN, but also reduced renal pathologic changes. L-N G-nitro arginine methylester (L-NAME) also reduced the contents of urinary NO3-/NO2- and the renal pathologic changes of rats with ATSN. CONCLUSION: The antiserum against rat complement C5b-9 complexes inhibited glomerular NO synthesis and glomerular mesangial cell proliferation of rats with ATSN.  相似文献   

19.
AIM: To clarify the protective effect of long-term administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin on ventricular remodeling after myocardial infarction (MI) in rats and its mechanisms. METHODS: Myocardial infarction were established by ligated left coronary anterior artery in SD rats, 24 hours after the operation, the survival rats were treated by gavage fluvastatin (20 mg·kg-1·d-1) or distilled water for 8 weeks. Doppler echocardiography, homodynamic and cardiac histomorphometry were used to assess the ventricular remodeling and cardiac function. The plasma levels of total cholesterol (Tch), creatinine (Cr), glutamic-oxal (o) acetic transaminase (AST), lipid peroxidation (LPO), glutathione perioxidase (GSH-PX), nitrogen monoxide (NO2-/NO3-) were detected. RESULTS: The Tch, Cr and AST were not significant difference in groups. Left ventricular end-diastole pressure, right relative weight, left ventricular posterior wall thickness, collagen volume fraction and the lung weight were decreased in AMI+fluvastatin group compared to AMI group (P<0.05, P<0.01); The levels of LPO, NO2-+NO3- in plasma and LPO in myocardium decreased, but plasma GSH-PX level increased in AMI+fluvastatin group (P<0.05). CONCLUSION: Fluvastatin ameliorates the ventricular structural remodeling in a rat model of infarction, and delays the development of heart failure. The anti-oxidation mechanism of fluvastatin may take part in this process.  相似文献   

20.
AIM: To investigate the effect of nitric oxide (NO) in ocular inflammation after intraocular lens implantation. METHODS: All New Zealand rabbits were divided randomly into three groups: 1. control group, 2. L-arginine (L-Arg) group, 3. N-nitro-L-arginine (L-NNA) group. Extracapsular cataract extraction (ECCE) and posterior chamber intraocular lens implantation (IOL) were operated in all animals of each groups. The inflammatory response of all rabbit eyes, including cornea edema and anterior chamber exudation were investigated 1, 3, 7, 14, 30 days afteroperation. Meanwhile, aqueous humor was drawn for white blood cell (WBC) counting and classifying, as well as for NO2-/NO3- measurement. RESULTS:NO2-/NO3- contents, total WBC and anterior chamber exudation in aqueous humor of L-Arg group were higher than that in control group. While that of L-NNA group were lower than that in control group.CONCLUSION:NO plays a role in intraocular inflammatory response after intraocular lens implantation. L-NNA, a nitric oxide synthase exhibitor, decreased NO contents, therefore it may reduce intraocular inflammatory response after intraocular lens implantation.  相似文献   

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