Leptin: an entry point for the treatment of peripheral tissue fibrosis and related diseases.

Leptin is a small peptide mainly secreted by adipocyte, which acts on the central nervous system of the hypothalamus to regulate the body's energy balance by inhibiting food intake, it also can directly act on specific cells through leptin receptors (for example, ObRa, which exists in the blood-brain barrier or kidneys), thereby affect cell metabolism. Excessive deposition of extracellular matrix (ECM) causes damage to normal tissues or destruction of organ structure, which will eventually lead to tissue or organ fibrosis. The sustainable development of fibrosis can lead to structural damage and functional decline of organs, and even exhaustion, which seriously threatens human health and life. In recent years, studies have found that leptin directly alleviates the fibrosis process of various tissues and organs in mammals. Therefore, we speculate that leptin may become a significant treatment for fibrosis of various tissues and organs in the future. So, the main purpose of this review is to explore the specific mechanism of leptin in the process of fibrosis in multiple tissues and organs, and to provide a theoretical basis for the treatment of various tissues and organs fibrosis and related diseases caused by it, which is of great significance in the future.

Preliminary investigation for effects of hypothalamic Leptin/Ghrelin and arcuate nucleus pro-opiomelanocortin system on regulation of high-altitude acclimatization.

This study aims to investigate the mechanism of hypothalamic Leptin/Ghrelin and arcuate nucleus pro-opiomelanocortin (POMC) system in the regulation of high-altitude acclimatization. SD rats (male) were divided into two groups and separately fed at the 2260m and 4700m altitude. Tow groups contained 5 small groups separately, including 1 d, 3 d, 7 d, 15 d and 30 d, and 8 rats in each group. Blood, cerebrospinal fluid and tissues were taken at setting time. Leptin and Ghrelin were detected by using radioactivity immuno-assay. RNA expression of NPY and POMC were detected by using RT-PCR assay. The number of NPY positive neurons was detected by using immunofluorescence (IF) and cell counting. Other rats were sent to the 4300m and fed in animal room with regular diet and drinking. The results indicated that after being sent to high altitude region, Leptin levels at the 3rd and 7th day were significantly higher than the 1st day, while decreased at 15th, and the level at 30th day was closed to the 1st day. Ghrelin levels decreased at the 3rd, 7th and 15th day, and were lower at the 30th day. Comparing to the 1st day, NPY transcription levels increased at the 7th day, while decreased at the 30th. POMC transcription level decreased at the 7th day, while increased at the 30th gradually. The feeding of the rats fed at the 4300m decreased at the 3rd and the 5th, while increased at the 7th, 15th and 30th day. The weight of the rats changed as the feeding changing. In conclusion, after being sent to the high region, the rats were adaptive to the hypoxia environment gradually, and the steady of neuro-endocrine regulation recovered or established.

[Effect of Tibetan medicine zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2].

To study the effect of Tibetan medicine Zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2, three different doses (1.2, 3.8 and 12 mg x kg(-1)) of Zuotai were administrated orally to rats once a day or once daily for twelve days, separately. Rats were administrated orally caffeine (CF) on the second day after Zuotai administration, and the urine concentration of CF metabolite 5-acetylamino-6-formylamino-3-methyl-uracil (AFMU), 1-methyluric acid (1U), 1-methylxanthine (1X), 1, 7-dimethylxanthine (17U) at 5 h after study drug administration was determined by RP-HPLC. The activity of CYP1A2 and NAT2 was evaluated by the ratio of metabolites (AFMU+1X+1U)/17U and the ratio of AFMU/(AFMU+1X+1U), respectively. The protein and mRNA expression of CYP1A2 and NAT2 were determined by ELISA and RT-PCR method, respectively. After single administration of Zuotai 3.8 mg x kg(-1) and repeated administration of Zuotai 3.8 and 12 mg x kg(-1), the activity of CYP1A2 and NAT2 decreased significantly compared with control group and there was no significant difference between other dose group and control group. The protein expression of CYP1A2 was significant lower than that in control group after repeated administration of Zuotai 12 mg x kg(-1), and the mRNA expression of CYP1A2 decreased significantly compared with that of control group after single administration of Zuotai 3.8 mg x kg(-1) and repeated admistration of Zuotai 12 mg x kg(-1), separately. The protein expression of NAT2 decreased significantly compared with that of control group after single and repeated administration of Zuotai 3.8 mg x kg(-1), respectively, and the mRNA expression of CYP1A2 decreased significantly compared with control group after single administration of Zuotai 3.8 mg x kg(-1). This study found that Tibetan medicine Zuotai had significant effect on the activity, protein and mRNA expression of CYP1A2 and NAT2.