孕酮对OCTN2的抑制作用及对左旋肉碱肾脏排泄的影响

目的 考察孕酮对肉碱/有机阳离子转运体2(carnitine/organic cation transporter 2,OCTN2)功能的影响,并探讨其是否通过抑制肾脏OCTN2功能改变左旋肉碱肾脏排泄,从而降低妊娠期血浆左旋肉碱浓度。方法 采用已构建的稳定高表达人OCTN2的MDCK-hOCTN2细胞模型,分别以米屈肼和氘代左旋肉碱为底物,考察孕酮对OCTN2的抑制作用。正常雌性ICR小鼠皮下注射孕酮,使其达妊娠晚期血清孕酮浓度,比较其与对照组小鼠左旋肉碱尿液排泄差异,以及血浆和各组织中左旋肉碱浓度差异。结果 孕酮显著抑制OCTN2对米屈肼和氘代左旋肉碱的摄取,半数抑制浓度分别为8.7 μmol·L^-1和14.0 μmol·L^-1。孕酮给药组小鼠血清孕酮浓度为462~1153 nmol·L^-1,与妊娠晚期生理浓度相当,左旋肉碱的尿液排泄量以及血浆、肝脏、肾脏和心脏中左旋肉碱浓度与对照组无显著差异。结论 孕酮显著抑制OCTN2功能,但与妊娠晚期生理浓度相当的孕酮不影响左旋肉碱的肾脏排泄及体内稳态。     

Modulation of drug block of the cardiac potassium channel KCNA5 by the drug transporters OCTN1 and MDR1

BACKGROUND AND PURPOSE

A common site for drug binding on voltage-gated ion channels is at the interior face of the channel pore. In this study, we tested the hypothesis that the extent of drug block of the human cardiac KCNA5 (K_v1.5) channel underlying the atrial-specific, ultra-rapidly activating, delayed K⁺ current (I_Kur) is modulated by the drug uptake and efflux transporters encoded by organic cation transporter 1 (OCTN1) and multiple drug-resistant gene 1 (MDR1) and expressed in human heart.

EXPERIMENTAL APPROACH

Drug block of KCNA5 was assessed in Chinese hamster ovary cells transiently transfected with KCNA5 alone or in combination with the OCTN1 or MDR1 transporter construct, as well as in an MDR1 stably expressed cell line.

KEY RESUTLS

Co-expression of OCTN1 significantly facilitated block by quinidine (10 µM), verapamil (20 µM), propafenone (5 µM) and clofilium (30 µM). Further evidence of drug transport modulating drug block was the finding that with OCTN1, block developed faster and only partially washed-out, and that block potentiation was prevented by cimetidine, an inhibitor of OCTN1. MDR1 expression attenuated KCNA5 block by erythromycin (an MDR1 substrate). Block was restored by reversin-205 (10 µM, an MDR1 inhibitor). MDR1 did not affect KCNA5 inhibition by KN-93 (1 µM), a blocker acting on the outer mouth of the channel pore.

CONCLUSIONS AND IMPLICATIONS

The extent of drug block of KCNA5 can be modulated by drug uptake and efflux transporters. These data provide further support for the idea that modifying intracellular drug concentrations could modulate the effects of blocking ion channels in patients.     

黄芩素自微乳的制备及大鼠体内生物利用度研究

目的:制备黄芩素自微乳化制剂(SMEDDS),考察其大鼠体内生物利用度。方法:采用伪三元相图法筛选自微乳的油相、表面活性剂及助表面活性剂;采用HPLC法测定大鼠血浆中药物浓度,与原料比较,对黄芩素自微乳进行大鼠体内生物利用度评价。结果:通过使用混合油相、混合表面活性剂及助表面活性剂,可获得较为理想的黄芩素自微乳。大鼠体内血药浓度-时间曲线结果表明,黄芩素自微乳的AUC是原料的3.77倍,且药时曲线的形状发生一定的改变。结论:自微乳系统可显著增加黄芩素的溶解度,有利于提高口服生物利用度,且自微乳可能改变其胃肠道吸收行为。     

Characterization of Calu-3 cell monolayers as a model of bronchial epithelial transport: organic cation interaction studies

Background: To fully exploit organic cation transporters for targeted drug delivery in the lung, the use of a readily available and well-characterized tissue culture model and cheap easily detectable substrates is indispensable.

Objectives: To investigate the suitability of Calu-3 as tissue model for characterizing organic cation permeation across the bronchial cells using a fluorescent dye, 4-(4-(Dimethylamino)styryl)-N-methylpyridinium iodide (4-DI-1-ASP).

Methods: Substrate uptake, inhibition, and transport were performed to establish active transport mechanism. Organic cation transporter expression was determined with quantitative polymerase chain reaction (qPCR), immune-histochemistry, and fluorescent microscopy.

Results: 4-Di-1-ASP uptake in Calu-3 cells was concentration (K_m = 2.7?±?0.3?mM, V_max = 4.6?±?2.6 nmol/µg protein/30?min), temperature (uptake at 37°C>>4°C), and pH dependent (higher uptake at pH ≥ 7). L-carnitine, verapamil, and corticosterone significantly inhibited its uptake with IC₅₀ of 28.2, 0.81, and 0.12?mM, respectively. Transport of the dye across the cells was polarized (AP→BL transport was 2.5-fold > BL→AP), saturable (Km = 43.9?±?3.2) (µM; Vmax =0.0228± nmol/cm²/sec) and reduced 3-fold by metabolic inhibition. The expression pattern of the organic cation transporters (OCT) and carnitine/organic cation transporter (OCTN) isoforms was: OCT1<<OCT3 <OCTN1<OCTN2; OCT2 was not detected.

Conclusions: Based on qPCR, immunohistochemistry, uptake and transport data, the Calu-3 cells can be used as a model for not only studying strategies for optimizing the effect of inhaled organic cations, but also for cross-validating newly-developed respiratory cell lines.     

A novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for improved stability and oral bioavailability of an oily drug, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol

To develop a novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for a water-insoluble oily drug, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) with improved stability and oral bioavailability, numerous S-SNEDDS were prepared with surfactant, hydrophilic polymer, antioxidant, and calcium silicate (porous carrier) using the spray-drying method. Their physicochemical properties were evaluated using emulsion droplet size analysis, SEM and PXRD. Moreover, the solubility, dissolution, stability, and pharmacokinetics of the selected S-SNEDDS were assessed compared with the drug and a commercial soft capsule. Sodium lauryl sulfate (SLS) and hydroxypropyl methylcellulose (HPMC) with the highest drug solubility were selected as surfactant and hydrophilic polymer, respectively. Among the antioxidants tested, only butylated hydroxyanisole (BHA) could completely protect the drug from oxidative degradation. The S-SNEDDS composed of PLAG/SLS/HPMC/BHA/calcium silicate at a weight ratio of 1:?0.25:?0.1:?0.0002:?0.5 provided an emulsion droplet size of less than 300?nm. In this S-SNEDDS, the drug and other ingredients might exist in the pores of carrier and attach onto its surface. It considerably improved the drug stability (about 100 vs. 70%, 60?°C for 5?d) and dissolution (about 80 vs. 20% in 60?min) compared to the commercial soft capsule. Moreover, the S-SNEDDS gave higher AUC, C_max, and T_max values than the commercial soft capsule; in particular, the former improved the oral bioavailability of PLAG by about 3-fold. Our results suggested that this S-SNEDDS provided excellent stability and oral bioavailability of PLAG. Thus, this S-SNEDDS would be recommended as a powerful oral drug delivery system for an oily drug, PLAG.     

Brain uptake and CNS levels of 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)urea (HECNU)

The uptake of ¹⁴C-labeled 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl) urea (HECNU) into the brain was investigated in the rat after intracarotid injection according to the method of OLDENDORF, as well as in cisternal cerebrospinal fluid obtained by suboccipital puncture after i.v. injection of the drug.The brain uptake index was 31.9 ± 2.9%. Cerebrospinal fluid/blood quotients after i.v. injection were 0.82 at 10 min and 1.10 at 60 min. The results of both methods clearly show that HECNU, in spite of its hydrophilic property, easily penetrates the blood-brain barrier.     

Characterization of the ERK1/2 phosphorylation profile in human and fish liver cells upon exposure to chemicals of environmental concern

We developed phospho-ERK1/2 ELISA for human and rainbow trout liver cells, employing HepG2 and RTL-W1 cell lines as models. The assay was applied to detect changes in ERK1/2 activity for nine chemicals, added over a wide concentration range and time points. Cell viability was measured to separate ERK1/2 regulation from cytotoxicity. Perfluorooctane sulfonate and carbendazim did not change ERK1/2 activity; influence on ERK1/2 due to cytotoxicity was indicated for tributyltin and cypermethrin. Mancozeb, benzo[a]pyrene, and bisphenol A stimulated ERK1/2 up to ∼2- (HepG2) and 1.5 (RTL-W1)-fold, though the kinetics differed between chemicals and cell lines. Bisphenol A and benzo[a]pyrene were the most potent concentration-wise, altering ERK1/2 activity in pM (HepG2) to nM (RTL-W1) range. While atrazine and ibuprofen increased ERK1/2 activity by ∼2-fold in HepG2, they did not initiate an appreciable response in RTL-W1. This assay proved to be a sensitive, medium- to high-throughput tool for detecting unrecognized ERK1/2-disrupting chemicals.     

Use of generally recognized as safe or dietary compounds to inhibit buprenorphine metabolism: potential to improve buprenorphine oral bioavailability

The present study evaluated the potential of five generally recognized as safe (GRAS) or dietary compounds (α‐mangostin, chrysin, ginger extract, pterostilbene and silybin) to inhibit oxidative (CYP) and conjugative (UGT) metabolism using pooled human intestinal and liver microsomes. Buprenorphine was chosen as the model substrate as it is extensively metabolized by CYPs to norbuprenorphine and by UGTs to buprenorphine glucuronide. Chrysin, ginger extract, α‐mangostin, pterostilbene and silybin were tested for their inhibition of the formation of norbuprenorphine or buprenorphine glucuronide in both intestinal and liver microsomes. Pterostilbene was the most potent inhibitor of norbuprenorphine formation in both intestinal and liver microsomes, with IC₅₀ values of 1.3 and 0.8 μM, respectively, while α‐mangostin and silybin most potently inhibited buprenorphine glucuronide formation. The equipotent combination of pterostilbene and ginger extract additively inhibited both pathways in intestinal microsomes. Since pterostilbene and ginger extract showed potent CYP and/or UGT inhibition of buprenorphine metabolism, their equipotent combination was tested to assess the presence of synergistic inhibition. However, because the combination showed additive inhibition, it was not used while performing IVIVE analysis. Based on quantitative in vitro–in vivo extrapolation, pterostilbene (21 mg oral dose) appeared to be most effective in improving the mean predicted F_oral and AUC_∞^PO of buprenorphine from 3 ± 2% and 340 ± 330 ng*min/ml to 75 ± 8% and 36,000 ± 25,000 ng*min/ml, respectively. At a 10‐fold lower dose of pterostilbene, the predicted buprenorphine F_oral approximated sublingual bioavailability (~35%) and showed a 2–4 fold reduction in the variability around the predicted AUC_∞^PO of buprenorphine. These results demonstrate the feasibility of using various GRAS/dietary compounds to inhibit substantially the metabolism by CYP and UGT enzymes to achieve higher and less variable oral bioavailability. This inhibitor strategy may be useful for drugs suffering from low and variable oral bioavailability due to extensive presystemic oxidative and/or conjugative metabolism.     

快速法检测抗-HIV(1+2)

目的探讨硒标法作为HIV(1 2)抗体检测酶联免疫吸附法(ELISA)阳性的标本送确证试验室作确证试验前进行一步筛查的实验方法的可行性。方法取2000年以来本中心ELISA检测初筛阴性、阳性标本与美国雅培公司生产的雅培DETERMINFHIV1／2试剂盒(硒标法)进行比较试验。结果硒标法检测抗-HIV(1 2)与HIV(1 2)抗体确证试验(WB)法之间有着很好的一致性。结论硒标法可作为艾滋病抗体确证试验检测前,初步筛查的另一原理的试剂使用。     

Effects of cytochrome P450 3A (CYP3A) and the drug transporters P-glycoprotein (MDR1/ABCB1) and MRP2 (ABCC2) on the pharmacokinetics of lopinavir

Background and purpose:

Lopinavir is extensively metabolized by cytochrome P450 3A (CYP3A) and is considered to be a substrate for the drug transporters ABCB1 (P-glycoprotein) and ABCC2 (MRP2). Here, we have assessed the individual and combined effects of CYP3A, ABCB1 and ABCC2 on the pharmacokinetics of lopinavir and the relative importance of intestinal and hepatic metabolism. We also evaluated whether ritonavir increases lopinavir oral bioavailability by inhibition of CYP3A, ABCB1 and/or ABCC2.

Experimental approach:

Lopinavir transport was measured in Madin-Darby canine kidney cells expressing ABCB1 or ABCC2. Oral lopinavir kinetics (+/− ritonavir) was studied in mice with genetic deletions of Cyp3a, Abcb1a/b and/or Abcc2, or in transgenic mice expressing human CYP3A4 exclusively in the liver and/or intestine.

Key results:

Lopinavir was transported by ABCB1 but not by ABCC2 in vitro. Lopinavir area under the plasma concentration – time curve (AUC)_oral was increased in Abcb1a/b^−/− mice (approximately ninefold vs. wild-type) but not in Abcc2^−/− mice. Increased lopinavir AUC_oral (>2000-fold) was observed in cytochrome P450 3A knockout (Cyp3a^−/−) mice compared with wild-type mice. No difference in AUC_oral between Cyp3a^−/− and Cyp3a/Abcb1a/b/Abcc2^−/− mice was observed. CYP3A4 activity in intestine or liver, separately, reduced lopinavir AUC_oral (>100-fold), compared with Cyp3a^−/− mice. Ritonavir markedly increased lopinavir AUC_oral in all CYP3A-containing mouse strains.

Conclusions and implications:

CYP3A was the major determinant of lopinavir pharmacokinetics, far more than Abcb1a/b. Both intestinal and hepatic CYP3A activity contributed importantly to low oral bioavailability of lopinavir. Ritonavir increased lopinavir bioavailability primarily by inhibiting CYP3A. Effects of Abcb1a/b were only detectable in the presence of CYP3A, suggesting saturation of Abcb1a/b in the absence of CYP3A activity.     

栀子苷通过抑制VPO1/ERK1/2信号通路减轻糖尿病心肌病大鼠的心肌细胞凋亡

目的:探讨栀子苷(geniposide,GE)改善大鼠糖尿病心肌病的作用及其具体机制。方法:24只成年雄性SD大鼠,随机分为3组:正常组(Control组,8只)、糖尿病心肌病组(DCM组,8只)、糖尿病心肌病组+栀子苷组(DCM+GE组,8只),采用高脂饲料联合链脲佐菌素(STZ)构建糖尿病心肌病大鼠模型,应用次氯酸(HOCl)诱导H9C2损伤模型。干预12周后,HE和Masson染色观察心脏组织病理学改变;TUNEL法检测大鼠心肌细胞凋亡水平;免疫组化检测及Western blot检测法检测VPO1/ERK1/2信号通路及凋亡相关蛋白表达水平。给予次氯酸刺激心肌细胞后,Western blot检测法检测ERK1/2、p-ERK1/2、Bcl-2、Bax蛋白表达水平的改变。给予ERK1/2酶抑制剂U0126后,用Western blot检测法再次检测ERK1/2、p-ERK1/2、Bcl-2、Bax蛋白表达水平的改变。结果:HE及Masson染色显示,与Control组相比,DCM组出现心肌纤维排列紊乱、心肌胶原含量明显增多,而DCM+GE组心肌损伤情况明显改善(P<0.05)。与Control组相比,DCM组心肌细胞凋亡水平及Bax/Bcl-2比值明显增加,而DCM+GE组心肌凋亡情况得到明显好转(P<0.05)。免疫组化和Western blot结果显示,在DCM组中VPO1、p-ERK1/2蛋白表达水平升高,而DCM+GE组中VPO1、p-ERK1/2蛋白表达水平得到了抑制(P<0.05)。进一步对H9C2细胞行HOCl干预发现,与Control组相比,次氯酸组出现p-ERK1/2蛋白表达水平及Bax/Bcl-2比值增加,而加入ERK1/2酶抑制剂U0126后p-ERK1/2蛋白表达水平及Bax/Bcl-2比值下降(P<0.05)。结论:栀子苷通过抑制VPO1/ERK1/2信号通路抑制心肌细胞凋亡从而改善糖尿病引起的心肌损伤。     

A further attempt to characterize the α2-adrenoceptor blocking properties of (imidazolyl-2)-2-benzodioxane 1–4 (170 150) in pithed rats

(Imidazolyl-2)-2-benzodioxane 1–4 (170 150) has been shown to possess α₂-adrenoceptor blocking properties. The present investigation attempted to further characterize the α₂-adrenoceptor blocking effect of 170 150. In pithed rats, 170 150 did not change the pressor effects of cirazoline a selective α₁-adrenoceptor stimulant. On the other hand, 170 150 significantly and competitively antagonized the effects of B-HT 933, B-HT 920 and clonidine, showing that it has a potent action on α₂-adrenoceptors since these three drugs act preferentially on α₂-adrenoceptors.     

D2 dopaminergic and 5-HT1A serotonergic activity of 2-(1-naphthyl)ethyl- and 2-(2-naphthyl)ethyl amines

Several tertiary 2-phenylethyl, 2-(1-naphthyl)ethyl and 2-(2-naphthyl)ethyl amines were synthesized and their binding affinities for dopamine D(1), D(2) and serotonin 5-HT(1A) receptors evaluated in radioligand binding assays. All compounds were inactive in D(1) dopamine radioligand binding assay. The 2-(1-naphthyl)ethyl analogues expressed a low but significant binding affinity for the D(2) and moderate one for the 5-HT(1A) receptor subtypes. Most of the remaining compounds expressed binding affinity at the 5-HT(1A) receptor subtype but were inactive in D(2) receptor binding assay. Based on these results and considering the chemical characteristics of the compounds synthesized and evaluated for dopaminergic and serotonergic activity throughout the present study it can be concluded that hydrophobic type of interaction (stacking or edge-to-face) plays a significant role in the formation of receptor-ligand complexes of 2-(1-naphthyl)ethyl amines. This structural motive can be applied to design and synthesize new, more potent dopaminergic/serotonergic ligands by slight chemical modifications.     

LC-MS/MS法研究1-[1-(6-甲氧基-2-萘基)乙基]-2-(4-硝基苄基)-6,7-二甲氧基-1,2,3,4-四氢异喹啉氢溴酸盐在大鼠体内的代谢产物

采用液相色谱-串联质谱法对大鼠灌胃1-［1-(6-甲氧基-2-萘基)乙基］-2-(4-硝基苄基)-6,7-二甲氧基-1,2,3,4-四氢异喹啉氢溴酸盐(编号P91024)后粪便、尿液、胆汁和血浆中的主要代谢产物进行研究。通过比较给药样品和空白样品的全扫描总离子流色谱和选择离子扫描色谱图差别寻找I相代谢产物；根据其一级和二级质谱图，确定I相代谢产物的分子结构。完全提取I相代谢产物后的样品溶液，再用葡糖醛酸酶酶解，得II相结合物的苷元部分，采用与I相代谢产物鉴定同样方法寻找和鉴定II相代谢产物苷元的结构，进而确证II相代谢产物的分子结构。从大鼠粪便中鉴定出P91024的2个I相代谢物，从胆汁中鉴定出1个I相和5个II相代谢产物，从尿液中鉴定出1个I相和3个II相代谢产物，从血浆中鉴定出4个I相和1个II相代谢产物；并分别分析推测出它们的结构。P91024在大鼠体内被代谢转化为多种产物，利用LC-MS/MS可以快速寻找和鉴定。     

1-(2,6-二甲氧基)-2-(3,4-二甲基苯乙氨基)丙烷盐酸盐(DDPH)拮抗α1肾上腺素受体的特性

目的　研究DDPH对α₁-肾上腺素受体(α₁-AR)及其亚型的拮抗作用。方法　放射配体结合实验和离体血管收缩功能实验。结果　DDPH对¹²⁵I-BE2254与大鼠脑皮质和脾脏α₁-AR结合呈竞争性拮抗作用。pK_I值在两者间无显著性差别, Hill系数均接近于1.0。在分别稳定表达α_1A,α_1B或α_1D-AR的克隆HEK293细胞中,其拮抗的pK_I值α_1A和α_1D比α_1B-AR高约2倍,Hill系数均接近于1.0。并拮抗去甲肾上腺素(NE)介导大鼠主动脉,肾动脉和脾脏收缩的pA₂值,在三者间无显著差别,斜率接近1.0。结论　DDPH对α₁-AR有竞争性拮抗作用,但其作用对α₁-AR亚型无选择性。     

Overexpression of SLURP-1 and -2 alleviates the tumorigenic action of tobacco-derived nitrosamine on immortalized oral epithelial cells

Recent research has demonstrated that mucocutaneous epithelial cells express functional nicotinic acetylcholine receptors (nAChRs) and that tobacco-derived carcinogenic nitrosamines, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and SLURP (secreted mammalian Ly-6/urokinase plasminogen activator receptor-related protein)-1 and -2 can act as non-canonical ligands of these receptors. It was found that recombinant SLURP-1 and -2 can lessen tumorigenic activity of nitrosamines. The immortalized esophageal keratinocytes (Het-1A cells) exhibit low SLURP-1 and -2 mRNA levels that decrease further after treatment with NNK. Based on these observations, we hypothesized that overexpression of full length SLURP proteins may protect Het-1A cells from malignant transformation by NNK. The Het-1A cells transfected with either SLURP-1 or -2 vector produced the highest amounts of respective proteins between 24 and 48 h, at which point they were exposed to 1 microM NNK for 24 h and their tumorigenic activities were subsequently evaluated by plating in soft agar and injecting subcutaneously to Nu/Nu mice. Transfection with either SLURP-1 or -2 cDNA in both cases significantly (p<0.05) diminished the number of colonies produced by NNK exposed cells. SLURP-1 was more efficient than SLURP-2 in abolishing the tumorigenic effect in nude mice. Thus, the anti-tumorigenic activities of SLURP-1 and -2 were demonstrated both in vitro and in vivo. The obtained results suggest that SLURP-like proteins may become useful for developing novel anti-cancer therapies.     

Elastic-contractile model proteins: Physical chemistry, protein function and drug design and delivery

This review presents the structure and physico-chemical properties of ECMPs, elastic-contractile model proteins using sparse design modifications of elastic (GVGVP)_n; it describes the capacity of ECMP to perform the energy conversions that sustain living organisms; it arrives at the hydration thermodynamics of ECMP in terms of the change in Gibbs free energy of hydrophobic association, ΔG_HA, and the apolar-polar repulsive free energy of hydration, ΔG_ap; it applies ΔG_HA, ΔG_ap, and the nature of elasticity to describe the function of basic diverse proteins, namely — the F₁-motor of ATP synthase, Complex III of mitochondria, the KscA potassium-channel, and the molecular chaperonin, GroEL/ES; it applies ΔG_HA and ΔG_ap to describe the function of ABC exporter proteins that confer multi-drug resistance (MDR) on micro-organisms and human carcinomas and suggests drug modifications with which to overcome MDR. Using ECMP, means are demonstrated, for quantifying drug hydrophobicity with which to combat MDR and for preparing ECMP drug delivery nanoparticles, ECMPddnp, decorated with synthetic antigen-binding fragments, Fab1 and Fab2, with which to target specific up-regulated receptors, characteristic of human carcinoma cells, for binding and localized drug release.     

1-(5-异喹啉磺酰基)-2-甲基哌嗪(H-7)对肺纤维化大鼠肺单核细胞趋化蛋白-1 mRNA表达的影响

研究蛋白激酶C(PKC)抑制剂 1 (5 异喹啉磺酰基 ) 2 甲基哌嗪 (H 7)对肺纤维化大鼠单核细胞趋化蛋白 1(MCP 1)mRNA表达的影响 ,为临床治疗肺纤维化提供理论基础 .博来霉素致大鼠肺纤维化动物模型 ,腹腔注射H 7后 ,定量RT PCR方法检测其对肺组织MCP 1mRNA表达的影响 ;测定实验组和对照组肺组织匀浆内羟脯氨酸的含量 ,观察肺组织病理学变化并计数单核细胞 .结果发现 ,H 7能显著抑制大鼠肺纤维化组织MCP 1mRNA表达和单核细胞的聚集以及羟脯氨酸的含量 .结果表明 ,H 7通过抑制肺组织MCP 1mRNA的表达 ,对博来霉素致肺纤维化有明显的防治作用 .