Anti-fibrotic Effect of Kudancao Tablets on Bleomycin-induced Pulmonary Fibrosis in Rats / 昆明医科大学学报

Objective To investigate the anti-fibrotic effect of Kudancao tablets on bleomycin-induced pulmonary fibrosis in rats . Methods Forty healthy adult SD rats(200±20g)were randomly divided into 4 groups: normal control group(without any treatment),normal saline group(intratracheal instillation of normal saline), model group(intratracheal instillation of 5mg/kg of Bleomycin)and kudancao tablets group(intragastric administration of kudancao tablets suspended in normal saline,0.705g/(100 g.d),2 times/day and for 5 times, then intratracheal instillation of 5 mg/kg of Bleomycin 1h later). Rats in all groups were scraficed 14d and 28d after intratracheal instillation. Alkali hydrolysis method was used to detect the HYP content in lung tissues. The pathological changes were observed with HE staining and silver staining. ResultsCompared with the normal control group and normal saline group,the HYP content in the lung tissues of rats in model group increased significantly (P<0.01). Compared with the model group,the HYP content in the lung tissues of rats in kudancao tablets group decreased significantly(P<0.01). Pathological examination showed that significant fibrotic changes were found in lungs of rats in model group,while the fibrotic changes were ameliorated in lungs of rats in kudancao tablets group. ConclusionKudancao tablets may decrease the hydroxyproline content in lung tissues,and ameliorate the fibrotic degree of lungs of rats with bleomycin-induced pulmonary fibrosis.

Differential expression of miRNAs in myocardial tissues of rats with lipopolysaccharide- induced endotoxemia / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the differential miRNA expression profile in the myocardium of rats with lipopolysaccharide (LPS)-induced endotoxemia and explore the role of miRNA in endotoxin-induced myocardial injury.</p><p><b>METHODS</b>Twenty male SD rats received intraperitoneal injection of 10 mg/kg LPS (n=10) or an equivalent amount of saline solution (n=10). At 24 h after LPS injection, the rats were sacrificed to detect myocardial expressions of TLR4, TNF-α and IL-1β using real-time PCR and for observing myocardial ultrastructures under transmission electron microscopy. The differentially expressed miRNA in the myocardium were detected using a miRNA array, and the common differentially expressed miRNAs were selected for verifying their actual expressions using real-time PCR.</p><p><b>RESULTS</b>TLR4, TNF-α and IL-1β were over-activated in the myocardium of LPS-treated rats, in which mitochondria swelling, structural damaged and cytoplasmic vacuoles were observed. In LPS-challenged rats, miR-194-3p, miR-344a-3p, miR-465-3p, miR-501-5p, miR-3596c, miR-185-3p, and miR-877 were found up-regulated significantly, whereas miR-208b-3p, miR-547-3p, miR-141-3p, miR-28-5p, and miR-3585-5p down-regulated in the myocardium.</p><p><b>CONCLUSION</b>Significant differential expression of the miRNAs occurs in the myocardium of LPS-treated rats, suggesting their involvement in endotoxin-induced myocardial injury.</p>

Relationship between adipose expression of 3-phosphoinositide-dependent protein kinase 1 and glycometabolism in a mouse model of hyperhomocysteinemia / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of homcysteine on the expression of 3-phosphoinositide-dependent protein kinase 1 (PDK1) in the adipose tissue and explore whether PDK1 inhibits p-Akt(Thr-308) expression and affect PI3K/Akt signal pathway to decrease glucose uptake and utilization.</p><p><b>METHODS</b>Forty mice were randomly divided into 4 groups (n=10), namely the fasting control group, feeding control group, fasting hyperhomocysteinemia group, and feeding hyperhomocysteinemia group. In the two hyperhomocysteinemia groups, the mice were given water containing 1.5% methionine to induce hyperhomocysteinemia. Blood glucose and insulin levels in each group were determined, and the expressions of PDK1 and Akt mRNA in the adipose tissue were detected using RT-PCR; the expressions of PDK1, p-Akt(Thr-308) and Akt proteins were detected using Western blotting.</p><p><b>RESULTS</b>In the fasting and feeding hyperhomocysteinemia groups, blood glucose and insulin levels were significantly higher than those in the two control groups. The expressions of PDK1 mRNA and PDK1 and p-Akt(Thr-308) proteins were reduced in the two hyperhomocysteinemia groups, but Akt mRNA and protein expressions were comparable with those in the control groups.</p><p><b>CONCLUSION</b>Homocysteine lowers the uptake and utilization of glucose by down-regulating PDK1 expression and affecting PI3K/Akt signal pathway to cause disturbance of glucose metabolism.</p>

Protective mechanisms of sevoflurane against one-lung ventilation-induced acute lung injury: role of cyclooxygenase-2 and 5-lipoxygenase pathways / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the protective mechanisms of sevoflurane against acute lung injury (ALI) induced by one-lung ventilation (OLV) in view of cyclooxygenase-2 (COX2) and 5-lipoxygenase (5-LOX) pathways.</p><p><b>METHOD</b>Eighteen healthy Japanese white rabbits were randomized into sham-operated group (S group), OLV group (O group) and OLV + sevoflurane group (OS group). COX2 and 5-LOX protein and mRNA expressions in the lungs were detected by Western blotting and real-time PCR, respectively. Prostaglandin I2 (PGI2), thromboxane A2 (TXA2) and leukotrienes B2 (LTB2) in the lung tissues were quantified with ELISA. Histological scores and lung wet/dry weight (W/D) ratios were determined for lung injury assessment.</p><p><b>RESULTS</b>COX2 and 5-LOX protein and mRNA expressions and the contents of LTB2, TXA2 and PGI2 in the lungs, lung W/D ratio and histological scores were significantly higher while PGI2/TXA2 ratio was significantly lower in O group and OS group than in S group (P<0.05). Compared with those in O group, COX2 and 5-LOX expressions, pulmonary contents of LTB2, TXA2 and PGI2, and lung W/D ratio all decreased significantly but PGI2/TXA2 ratio was significantly elevated in OS group (P<0.05).</p><p><b>CONCLUSION</b>OLV may activate COX2 and 5-LOX pathways to result in increased production of arachidonic acid metabolites. Sevoflurane protects against OLV-induced ALI probably by reducing AA metabolites and regulating PGI2/TXA2 ratio through inhibitions of COX2 and 5-LOX pathways.</p>

Effects of sevoflurane on pulmonary cytosolic phospholipase A₂ and clara cell secretory protein expressions in rabbits with one-lung ventilation-induced lung injury / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of sevoflurane on cytosolic phospholipase A₂ (C-PLA₂) and clara cell secretory protein (CCSP) in lung tissues of rabbits with one-lung ventilation (OLV)-induced lung injuries.</p><p><b>METHODS</b>Thirty-six healthy Japanese white rabbits were randomized into sham-operated group, OLV group, and OLV plus sevoflurane group subdivided into 4 subgroups with sevoflurane concentrations of 1%, 2%, 3% and 4%. CCSP and C-PLA₂ mRNA and protein expressions in rabbit lung tissues were detected by Western blotting and real-time PCR, and the content of arachidonic acid (AA) was measured using ELISA. The severities of the lung injury were evaluated according to lung wet/dry weight (W/D) ratio and histological scores.</p><p><b>RESULTS</b>In the OLV group and OLV+ sevoflurane groups, pulmonary CCSP expressions were significantly lower, while C-PLA₂ expression, lung W/D ratios and lung histological scores were significantly higher than those in the sham-operated group (P<0.05). Compared with OLV group, the OLV+sevoflurane groups showed significantly increased expressions of CCSP and reduced C-PLA₂ expression, lung W/D ratios and histological scores (P<0.05). In the 4 OLV+sevoflurane groups, CCSP expressions underwent no significant changes as sevoflurane concentration increased, but C-PLA₂ expressions, lung W/D ratios and histological scores all decreased gradually as the concentrations of sevoflurane increased (P<0.05).</p><p><b>CONCLUSION</b>OLV can result in down-regulated CCSP expressions and up-regulated C-PLA₂ expressions in rabbit lung tissues. Sevoflurane can protect against OLV-induced acute lung injury possibly by inhibiting C-PLA₂ expression via up-regulation of CCSP expressions or through other mechanisms resulting in down-regulated expression of C-PLA₂.</p>

Effects of interleukin-17 on murine pulmonary fibroblast proliferation, transformation and collagen synthesis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of interleukin-17 (IL-17) on the proliferation, transformation and collagen synthesis of the lung fibroblasts in mice with bleomycin-induced pulmonary fibrosis.</p><p><b>METHODS</b>In a mouse model of pulmonary fibrosis established by intratracheal administration of 5 mg/kg bleomycin, the dynamic expressions of IL-17/IL-17 receptor (IL-17R) mRNAs were detected by RT-PCR. At 14 days following bleomycin administration, the pulmonary fibroblasts were isolated, cultured and identified. MTT assay was used to assess the proliferation of the pulmonary fibroblasts in response to IL-17 treatment at different concentrations, and RT-PCR and Western blotting were employed to examine the mRNA and protein expressions of α-smooth muscle actin (α-SMA) and types I and III collagen.</p><p><b>RESULTS</b>IL-17/IL-17R mRNA levels were increased obviously in the pulmonary fibroblasts of rats with pulmonary fibrosis, and the highest expressions occurred at 14 days following bleomycin administration. Exogenous IL-17, at the optimal concentration of 50 ng/ml, significantly promoted the proliferation of the pulmonary fibroblasts in primary culture and obviously increased α-SMA expression and types I and III collagen synthesis in the fibroblasts.</p><p><b>CONCLUSION</b>IL-17 can promote the proliferation, transformation, and collagen synthesis of the pulmonary fibroblasts from rats with bleomycin-induced pulmonary fibrosis.</p>

Paragonimus worm from a New Guinea native in 1926

OBJECTIVE@#To reobserve and research the specimen of Paragonimus worm found in the left lung of a New Guinea native in 1926, which was previously identified as Paragonimus westermani Kerbert or Paragonimus ringeri Cobbold.@*METHODS@#Using reconstructive software and microscopy to observe some organs of the worm, and compared with other species of paragonimus.@*RESULTS@#The three dimensional (3D) views of ovary and two testes of New Guinea specimen showed that the ovary was clearly divided into six lobes. These two testes were situated oppositely in the body. One teste was divided into four branches, while another was divided into five. The cuticular spines were arranged in groups over the entire skin covered in a slide, each group was consisted of two to four single spine.@*CONCLUSIONS@#Based on 3D views and measurements, we reclassified it as Paragonimus siamensis. This was also the first report of human case infected by Paragonimus siamensis.

Expression of peptide transporter 2 mRNA in lungs of rats with lipopolysaccharide-induced acute lung injury / 中国药理学与毒理学杂志

AIM To investigate the expression of pep-tide transporter (PEPT)2 mRNA in the lungs of ratswith lipopolysaccharide(LPS)-induced acute lung inju-ry. METHODS Health male Sprague-Dawley rats were divided randomly into 5 groups: normal control,cheally) given groups. Lung histopathological changes were observed under light microscope. Lung wet-to-dry weight (W/D) ratios, total protein concentration in bronchoalveolar lavage fluid (BALF) and lung my-eloperoxidase(MPO) activity were measured. The ex-pression levels of PEPT2 mRNA were evaluated by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS Typical pathological inflammation changes in the lungs, including alveolar congestion, hemorrhage, edema, infiltration of neutro-phils in the air space or vessel wall, thickness of the alveolar wall, and hyaline membrane formation, were observed in LPS groups. The lung W/D ratios in LPS 2, 4 and 8 h groups (4.72±0.18, 5.06±0. 17 and 5.12±0.16) were significantly higher than those innormal control and saline groups (4.12±0. 15 and 4.14±0.11). Compared with normal control and sa-g-1 wet tissue], MPO activity increased obviously in LPS2,4 and 8 h groups[(1.96±0.15), (2.23±protein concentration in BALF in LPS 2, 4 and 8 hgroups [ (36.6±2.9), ( 86.9±3.5 ) and (92.2±There was no statistical difference in PEPT2 mRNA levels in the lungs of rats among all groups. CON-CLUSION PEPT2 mRNA level does not change sig-nificantly in the acute injured lung tissue induced by LPS.

Role of Oxygen Free Racical in the Proliferation of ECV304 Induced by AngⅡ / 昆明医科大学学报

Objective To explore the role of oxygen free radicals in the proliferation of ECV304 induced by AngⅡ.Methods The lines of human umbilical vein endothelial cell(ECV304)cultured in vivo were divided into three groups which were treated by AngⅡ,AngⅡ+N-acetyl-L-cysteine(NAC),and normal culture medium.First we observed the proliferous effect of ECV304 induced by AngⅡat different concentration with improved MTT and microscope.Then the contents of oxygen free radicals(?OH)in three groups were detected by spectrophotometer.Results ECV304 incubated with AngⅡ(0.03125～1?mol/L)for 12 hours increased the proliferation rate(P 0.05 vs.control group).Conclusions ECV304 induced by AngⅡcan produce oxygen free radicals(?OH),and the contents of oxygen free radicals(?OH) increase with the prolongation of time and the enlargement of dose;Antioxidant NAC can inhibit the proliferation of ECV304 induced by AngⅡ,this effect may be related with reducing the content of oxygen free radicals(?OH);oxygen free radicals(?OH)may be one of the major mocleculars which play an important role in the signal transduction of ECV304 proliferation.

Pulmonary Peptidomimetic Drug and Peptide Transportand Peptide Transporters / 昆明医科大学学报

Recent studies show that peptide transporters expressed in respiratory tract play a major role in pulmonary peptidomimetic drug and peptide transport.In this article we reviewed the structure,localization,function and the transport mechanism of peptide transporters.

On the Negative Effects of the Evaluation Function of Core Journals / 昆明医科大学学报

As a tool for the research of periodical literature data,core journal was initially used in optimizing selection of journals for libraries and information institutes and in providing access for readers to selection of journals.But in recent years,the primitive function of core journal has began to weaken and its negative effects to generalize,mainly in the value orientation deviation of academic periodicals and in the generalization of the evaluation function.Due to these effects,bad results have emerged in periodical circle,academia and even in scientific research management,therefore,rational cognition may be required on the functional effects of core journals.

Hepatolenticular Degeneration Is Disease Due to Toxin-pathogen Invading Collaterals / 中华中医药杂志

Hepatolenticular degeneration,namely Wilson's disease,an autosomal recessive disorder of copper metabolism.The author of this article gave a definition to toxin-pathogen,discussed the basic concept of collaterals disease briefly.And pointed out that hepatolenticular degeneration is a disease due to toxin-pathogen invading collaterals,which was caused by disorder of copper metabolism.This can result in toxin stagnating in collaterals and stagnation of blood stasis in collaterals in the initial stage,and collaterals injured at last.To improve QI-blood circulation and regulate the function of zang fu is important in order to accelerate elimination of toxin and prevent copper from stagnating. Specific therapy vary according to different clinical symptoms,such as promoting blood circulation for removing obstruction in collaterals and clearing toxin, clearing heat-fire and clearing toxin and dispersing stagnated liver-qi for promoting bile flow et al.

Diagnosis and treatment of two cases of flaccidity syndrome by professor CHEN Jin-liang / 中华中医药杂志

We treated two cases of flaccidity syndrome,one who was suffering obstinate myasthenia gravis was treated by modified Mahuang Fuzi Xixin decoction which is based on warming Yang and replenishing qi,dredging the meridian passage.The other who was suffering lipid storage myopathy was treated by modified Buzhong Yiqi decoction which is based on strengthening spleen and improving digest,ascending the clear and descending the turbid,supplementing qi and nourishing blood, promoting blood circulation to remove meridian obstruction.Both got the obvious improvement.

Effect of cholecystokinin-octapeptide on changes in rabbit pulmonary artery reactivity induced by tumor necrosis factor-alpha in vitro and the preliminary study of its mechanisms / 中国病理生理杂志

AIM：The mechanism of tumor necrosis factor-alpha (TNF-α) induced pulmonary artery hypertension(PAH) in endotoxic shock (ES) is not clear. Cholecystokinin-octapeptide (CCK-8) had anti-ES and anti-PAH effects. The impact of CCK-8 on changes in vascular reactivity and endothelial ultrastructure induced by TNF-α was studied. The role of nitric oxide (NO) was preliminarily studied. METHODS：Rabbit pulmonary artery rings were divided into four groups: TNF-α, TNF-α+CCK-8, CCK-8 and Vehicle. The rings were incubated for 2 h, 7 h or 14 h. Relaxative responses to ACh(10-8-10-5 mol/L)， SNP (10-9-10-6 mol/L) and contractile responses to PE(10-8-10-5 mol/L) were generated seperately. The NOS activity of rings was detected and the ultrastructure of endothelium was observed in the groups that incubated for 7 h.RESULTS:The relaxative responses to ACh were not affected by TNF-α and CCK-8 after incubation for 2 h. TNF-α(7 h,14 h) significantly reduced ACh-induced endothelium-dependent relaxation response of pulmonary artery. CCK-8 reversed the effect. CCK-8 itself had no effect on responses of normal pulmonary artery. Contraction to PE and relaxation to SNP were unaffected by TNF-α, CCK-8. The NOS activity increased in the TNF-α and the TNF-α+CCK-8 groups. While no significant difference was obseved between the Vehicle and the CCK-8 groups. Endothelial injury in TNF-α group and alleviated changes in TNF-α+CCK-8 group were observed. CONCLUSION:TNF-α significantly inhibits endothelium-dependent relaxation, which be one of the mechanisms of PAH induced by TNF-α during ES. It was found for the first time that CCK-8 reversed TNF-α induced impairment of endothelium-dependent relaxation and alleviated structural injury of endothelium, which might be one of the mechanisms of anti-PAH effect by CCK-8 during ES. The effects of TNF-α and CCK-8 might be related to NO.

The augmentative effect of inducible nitric oxide synthase on pulmonary fibrosis progression / 中国病理生理杂志

AIM: To study the up-regulation of inducible nitric oxide synthase (iNOS) in lung of pulmonary fibrosis and its relationship with fibrosis. METHODS: The changes of amount of iNOS positive stain cells and type Ⅰ?Ⅲ collagen were examined on the day 7, 14 and 30 after intratracheal administration of bleomycin A_5. The contents of NO-_2/NO-_3 (nitrite/nitrate) in out-flowing pulmonary blood (OPB), hydroxyproline in lung and the histological changes were detected after iNOS was blocked by aminoguanidine (AG). RESULTS: (1) The number of iNOS-positive stain cells increased significantly in BLMA_5 7 d, 14 d and 30 d groups compared with that in control group (P

Role of nitric oxide in the inhibition of lipopolysaccharide-induced thoracic aortic hyporeactivity by cholecystokinin in vitro / 中国病理生理杂志

AIM: To investigate the effect of cholecystokinin octapeptide(CCK-8) on the L-arginine-nitric oxide(NO) pathway in rabbit thoracic aortae treated with lipopolysaccharide(LPS). METHODS: The isolated thoracic aortic rings(TARs) from rabbits were incubated with LPS, LPS+CCK or vehicle for 14 h. Then the contractility to phenylephrine(PE) by TARs and the response to L-arginine(L-Arg) by pre-contractile TARs were measured. In addition, we added NO synthase(NOS) inhibitors aminoguanidine(AG)and N ?-nitro-L-arginine(L-NNA) into organ baths to observe the changes of vascular contractility to PE. NOS activity in isolated TARs were also detected. RESULTS: Incubation of TARs with LPS for 14 h resulted in an increase of NOS activity and a reduction of contractility to PE. Treatment with CCK-8 significantly inhibited the increased NOS activity in thoracic aortae and improved the hypocontractility of TARs to the same degree as AG. CONCLUSION: CCK-8 may improve the hypocontractility of TARs induced by LPS by inhibiting the activity of NOS.

Effects of cholecystokinin octapeptide on changes in rabbit thoracic aortic reactivities induced by lipopolysaccharides in vitro / 中国病理生理杂志

AIM and METHODS: To elucidate the mechanism of anti-endotoxic shock of cholecystokinin octapeptide(CCK-8), the effects of CCK-8 on changes in rabbit thoracic aortic reactivities induced by lipopolysaccharides(LPS) in vitro were studied, and the ultrastructure of the endothelial cells was observed under scanning electron microscope. RESULTS: Incubation of thoracic aortic rings(TARs) with LPS(100 mg/L) resulted in an time-dependent impairment of the endothelium-dependent relaxations to acetylcholine(incubation for 3, 7, 14 h), a reduction of contractive response to phenylphrine(incubation for 14 h) and ultrastructural injury in endothelial cells(incubation for 7 h), all of which were alleviated by concomitant incubation with CCK-8(1 mg/L). In contrast, neither the vascular contractions nor the relaxations were affected by CCK-8 (1 mg/L) alone. CONCLUSION: CCK-8 improved the vascular reactivities in the presence of LPS, which may be one of the anti-endotoxic shock mechanisms of CCK.

Mechanism of exogenous nitric oxide in attenuating endotoxin-induced increase of rat pulmonary microvascular permeability / 中国病理生理杂志

AIM and METHODS: The animal model of acute lung injury (ALI) caused by intratracheal instillation of lipopolysaccharides(LPS) in vivo and human peripheral blood polymorphonuclear neutrophil (PMN) in vitro were used to study the effects of sodium nitroprusside (SNP), nitric oxide (NO) donor, on LPS-induced PMN accumulation, microvascular permeability and PMN apoptosis. RESULTS: ① In vivo , PMN accumulation in lung, the protein content in bronchoalveolar lavage fluid (BALF) and the Evans blue dye and monastral blue dye extravasation in lung tissue of LPS group were markedly higher than those of both sham operation group and LPS+SNP group. ② In vitro, the apoptotic percentage of SNP group was much higher than that of control group, while compared with LPS group, SNP+LPS group has significantly higher apoptotic percentage. CONCLUSIONS: SNP intratracheal instillation attenuated LPS-induced microvascular permeability and alleviated ALI. PMN apoptosis induced by SNP may be one of the potential mechanisms underlying the decrease of PMN accumulation in lung tissue.

Effect of nitric oxide on proteinuria excretion in rats suffering from renal ischemia-reperfusion / 中国病理生理杂志

AIM: To investigate the urinary protein (UP) excretion in rats suffering from renal ischemia-reperfusion (I-R) and effect of nitric oxide on it. METHODS: SD rats were used to establish the renal I-R model. Sodium nitroprusside (SNP), N ?-nitro-L-arginine (L-NNA) and aminoguanidine (AG) were used to determine the effect of nitric oxide on UP excretion under renal I-R. Quantitative analysis of UP was made by chromatometry. UP species were separated by SDS-PAGE. RESULTS: Renal I-R caused significant increase in UP ( P

Effect of interleukin - 10 on attenuating endotoxin - induced acute lung injury / 中国病理生理杂志

AIM: To study the role of polymorphonuclear neutrophile(PMN) in lipopolysaccharide (LPS)- induced acute lung injury (ALI) and the protective effect of interleukin - 10(IL - 10) on ALI. METHODS: LPS alone (100 ?g) or LPS+ IL-10 (l ug) was instilled intratracheally into rats. PMN numbers, protein content and malondialdehyde (MDA) content in bronchoalveolar lavage fluid (BALF) were measured. Histological change of lung was also observed. RESULTS: LPS increased significantly PMN numbers, protein content and MDA content in BALF. Histological finding shows PMN accumulation in lung. IL - 10+LPS reduced remarkably PMN numbers ,pro- tein content and MDA content in BALF than those caused by LPS. PMN decreasing was also identified by light microscopy. CONCLUSION: LPS instilled intratracheally causes PMN accumulation in lung and ALI, while IL - 10 could alleviate ALI through reducing PMN accumulation.