[Effect of compound qingqin liquid on the expression levels of ang II and COX-2 mRNA transcription and protein expression in the renal tissue of uric acid nephropathy rats: an experimental study].

OBJECTIVE: To investigate the effect of Compound Qingqin Liquid (CQL) on the expression level of angiotensin II (Ang II) and COX-2 mRNA transcription and protein expression in the renal tissue of rats with uric acid nephropathy. METHODS: SD rats were randomly divided into the blank control group, the model group, the positive drug group, the high, moderate, and low dose CQL group according to number randomization principle. The model was established by gastrogavage of adenine, accompanied with yeast feeding. Distilled water was given by gastrogavage to rats in the blank control group and the model group. Allopurinol at the daily dose of 9.33 mg/kg was given by gastrogavage to rats of the positive control group. CQL at the daily dose of 3.77 g/kg, 1.89 g/kg, and 0.09 g/kg was respectively given by gastrogavage to rats in the high, moderate, and low dose CQL groups. All treatment lasted for 6 weeks. Rats were randomly divided at week 4 (3 in the blank control group, and 6 in the rest groups), and the rest rats were killed at week 6. The renal tissue was extracted. The expression level of Ang II and COX-2 mRNA transcription were detected by RT-PCR. The expression level of Ang II was detected by ELISA. The expression level of COX-2 protein was detected by Western blot and immunohistochemical assay. RESULTS: Compared with the blank control group, except the mRNA expression of Ang II at week 4, the mRNA and protein expression of Ang II and COX-2 obviously increased at week 4 and 6 in the model group (P < 0.01, P < 0.05). The COX-2 protein expression at week 4 was obviously lower in the high and moderate dose CQL groups than in the model group and the low dose CQL group (P < 0.05); the average integral of optical density value was obviously lower in the positive control group than in the model group. Except the mRNA expression of Ang II in the high dose CQL group at week 6, the mRNA and protein expression of Ang II obviously decreased in the positive control group and each dose CQL group (P < 0.01, P < 0.05). Of them, the effects were better in the high and moderate dose CQL groups than in the positive control group and the low dose CQL group (P < 0.05, P < 0.01). Besides, the mRNA expression of COX-2, the average integral of optical density value were obviously lower in the positive control group and each dose CQL group than in the model group (P < 0.05). The protein expression of COX-2 was obviously lower in the high and moderate dose CQL groups than in the model group (P < 0.05). Of them, the mRNA expression of COX-2 was better in the moderate dose CQL group than in the positive control group (P < 0.05); the protein expression of COX-2 was better in the high dose CQL group than in the low dose CQL group (P < 0.05). CONCLUSION: CQL was capable of lowering the expression level of Ang II, COX-2 mRNA transcription and protein expression, thus suppressing the inflammatory pathological injury of the renal tissue.

[Effect of compound qingqin liquid on the expression of toll-like receptor in the renal tissue of rats with urate nephropathy].

OBJECTIVE: To investigate the effect of compound qingqin liquid (CQL) on Toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) in rats with urate nephropathy, and to explore its renal protection mechanism. METHODS: Totally 55 SD rats were randomly divided into 5 groups, i.e., the normal control group (n =5), the model group (n =10), the positive drug group (n=10), and the high-, medium-, low-dose CQL groups (n=10) respectively. The urate nephropathy model was induced by intragastrically administering adenine and feeding yeast. Distilled water was intragastrically administered at the daily dose of 10 mL/kg to rats in the normal control group and the model group. Allopurinol was intragastrically administered at the daily dose of 9.33 mg/kg to rats in the positive control group. CQL was intragastrically administered at the daily dose of 3.77, 1.89, 0.94 g/kg to rats in the high-, medium-, and low-dose CQL groups. Rats of each group were executed in batches at the 4th and 6th week respectively. Their kidney tissues were taken out to determine the mRNA transcription level of TLR2 and TLR4 by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression level of TLR2 and TLR4 were determined by Western blot. The protein expression level of TLR4 was also detected by immunohistochemical assay. RESULTS: At week 4 and 6, the protein expression of TLR2 and TLR4 as well as the mRNA transcription of TLR4 increased in the model group, when compared with the control group (P < 0.05, P < 0.01). Compared with the model group, there was no statistical difference in the transcription level of TLR2 mRNA or TLR4 mRNA among the 3 CQL groups (P > 0.05) at week 4 and 6. Additionally, at week 6, the protein expression of TLR4 and TLR2 could be reduced by CQL (P < 0.05, P < 0.01). CONCLUSION: CQL might protect kidney tissue against inflammatory injury by inhibiting the protein expression levels of TLR2 and TLR4.

[Effect of shengbanfang on CYP3A1 activities of Sprague-Dawley rat].

OBJECTIVE: To study the influences of Shengbanfang on CYP3A1 activities of SD rat and provide suggestions for drug combinations. METHODS: 25 male SD rats were devided into 5 groups randomly,and treated with saline( NS, ig, 10 mg/(kg/d) ,qd,14 d), dexamethasone (DEX, ig, 100 mg/(kg x d), qd, 3 d), high dose of Shengbanfang (HD, ig, 8.645 g/kg, bid, 14 d), middle dose of Shengbanfang (MD, ig, 4.322 g/kg, bid, 14 d) and low dose of Shengbanfang (LD, ig, 2.161 g/kg, bid, 14 d), respectively. The HPLC method was established and validated to determine the productive velocity of 6beta-hydroxytestosterone and measure the activity of CYP3Al. RESULTS: Under the optimized incubation conditions, the productive rates of 6beta-hydroxytestosterone of HD, MD, LD, NS and DEX, groups were (55.82 +/- 5.97), (65.10 +/- 6.83), (60.89 +/- 6.53), (62.17 +/- 6.55), (126.73 +/- 15.40) micromol/(L x mg pro x min). There were significant differences between Shengbanfang groups compared with dexamethasone group, but there was no significant difference between Shengbanfang groups and the control group (NS). CONCLUSION: Shengbanfang has no induce effect on the enzymic activity of CYP3Al in SD rats.

[Exploring the potential molecular target proteins of yinchenhao decoction using computer systemic biology].

OBJECTIVE: To predict the potential molecular target proteins of Yinchenhao decocation by computer systems biology approaches. METHODS: For text mining, TCMGeneDIT was used to retrieve association information regarding genes or proteins, Artemisiae scopariae of 17 main compounds absorbed into blood after oral administration of Yinchenhao decoction, target identificetion and analysis was conducted to determine the target proteins of those compounds using PharmMapper sever. The proteins which had direct interaction with predictive target proteins were selected by screening BIND, BioGRID, DIP, HPRD, IntAct, MINT database. RESULTS: Four and eight proteins were found to respectively associate with Artemisiae scopariae herba and Rhei radix et rhizome. Six components including rhein, emodin, 6, 7-dimethoxy coumarin not only directly interacted with target proteins which were proved by experiments, but also interacted with other related proteins. Eight components such as isofradin-3-O-glycoside could only play assistant roles by interacting with related proteins. CONCLUSION: The result provides useful information for further research. It is expected it would be helpful for understanding the molecular mechanism of Yinchenhao decoction. Taken together, the protocol developed in the study may lead to a deeper understanding of a system as a whole in the mechanism of Chinses formula.

[Preparation of docetaxel liposomes and their pharmacokinetics in rabbits].

BACKGROUND & OBJECTIVE: Docetaxel is used to treat non-small cell lung cancer, breast cancer and ovarian cancer. It is indissolvable and the solvent containing polysorbate-80 and 13% solution of ethanol is used for injections. Its clinical application is limited because of frequent severe hypersensitive responses. This study was to prepare docetaxel (DOC) liposomes and investigate their pharmacokinetics in rabbits after intravenous administration. METHODS: DOC liposomes, with or without modification of polyethylene glycol (PEG), were prepared by thin-film ultrasonic dispersion method. The entrapment efficiency and mean diameter of the liposomes were measured. After intravenous administration in rabbits, plasma DOC concentration was detected by solid phase extraction high-performance liquid chromatography (SPE-HPLC). The pharmacokinetic parameters were calculated and analyzed by 3p87 pharmacokinetic program. RESULTS: The entrapment efficiency of DOC liposomes was above 75%. The mean diameter was about 150 nm. The half-life of distribution (T(1/2alpha)) were (0.17+/-0.04) h for market docetaxel injection (M-DOC), (0.31+/-0.11) h for common DOC liposome (L-DOC), and (0.32+/-0.06) h for PEG-2000-modified DOC long circulating liposome (PEG-DOC-LCL); the half-life of clearance (T(1/2beta)) were (8.54+/-1.05), (11.18+/-1.33), and (10.51+/-1.13) h, respectively; the apparent volume of distribution (V(d)) were (13.66+/-3.62), (8.65+/-1.11), and (6.31+/-0.55) L, respectively; the area under the concentration-time curve from 0 to 24 h (AUC(0-->24)) were (13.45+/-2.44), (22.83+/-3.57), and (29.31+/-5.96) mg x (h x L)(-1), respectively; the area under the concentration-time curve from 0 to infinity h (AUC(0-->infinity)) were (15.07+/-2.76), (28.70+/-4.95), and (36.95+/-9.13) mg x (h x L)(-1), respectively; the clearance (CL) were (1.10+/-0.18), (0.54+/-0.08), and (0.42+/-0.07) L/h, respectively. CONCLUSION: The thin-film prepared DOC liposomes have high entrapment efficiency and small particle size. Both liposomes, especially PEG-DOC-LCL, can raise AUC and prolong the resident time of drugs in the blood circulating system.

[Analysis of antineoplastic drugs used in Cancer Center, Sun Yat-sen University, during the period of 1996-2005].

BACKGROUND & OBJECTIVE: Lately, the prevention, treatment and research of cancer have developed rapidly. Antineoplastic drugs have become one of the major measures for cancer therapy. Many new antineoplastic drugs have been discovered and prepared, and used to treat tumors. Cancer Center of Sun Yat-sen University is one of the biggest cancer hospitals in South China. The use of antineoplastic drugs of this center can reflect changes in this area. This study was to analyze and evaluate the situation and trend of antineoplastic drugs used in Cancer Center, Sun Yat-sen University from 1996 and 2005, in order to provide references for the rational use of drugs in clinical application. METHODS: Consumption of antineoplastic drugs was analyzed by sum and defined daily dose (DDDs) ranking. RESULTS: The costs of antineoplastic drugs occupied 31.0%-48.8% of all drugs from 1996 to 2005; and the average increasing ratio is 21.5%. The cost rate of anti-cancer vegetable drugs and other genus increased the quickest, while the total costs of alkylate increased the slowest during the ten years. Some new monoantibodies and gene drugs were continuously applied in clinical use. CONCLUSION: The direction of the research and development of antineoplastic drugs is towards high efficiency, low toxicity and individualized use.