Study Of The Characteristics Of Tcm Syndromes And Treatment Of Male Infertility, And Semen Metabonomics In Kidney-yang Deficiency Syndrome

[Objective] To analyze and summarize the characteristics of TCM syndromes and treatment of male infertility resulting from non-liquefaction of semen via TCM literature reading, and further investigate the characteristics of semen metabolomics in male infertility due to kidney-yang deficiency and its important metabolic pathways to elucidate the pathogenesis of kidney-yang deficiency-typed male infertility.[Methods] The related literature concerning male infertility with syndrome differentiation, TCM therapy for male infertility, and TCM therapy for male infertility resulting from non-liquefaction of semen from2002-2012were obtained from the CNKI database and a new database was set up. Common TCM syndrome elements were summarized via frequency analysis. The medication for male infertility patients with TCM syndromes such as kidney-yang deficiency, kidney-yin deficiency, accumulated dampness-heat, spleen-kidney-yang deficiency or fire excess from yin deficiency were analyzed with a TCM correlation analysis software. The medication and TCM syndromes with semen non-liquefaction were also analyzed and summarized. Semen samples of fertility male and infertility male with kidney-yang deficiency were collected from the Shanghai Human Sperm Bank and Andrology Outpatient Service respectively. Total ions chromatogram of semen in both groups was detected by LC-MS and different metabolites were found via principal component analysis. Other multivariate statistical analytical methods were used here to determine the metabolic pathway.[Results](1) A tpassages of literature related to male infertility TCM syndrome differentiation, and the total emerging frequency was431. The syndromes with frequency over2%were as follows:kidney-yang deficiency (14.85%), kidney-essence deficiency (12.99%), kidney-yin deficiency (7.43%), kidney deficiency (6.73%), dampness-heat diffusing down (6.73%), asthenia of both the spleen and kidney (3.94%), yin deficiency (3.71%), kidney-qi deficiency (3.25%), spleen and kidney yang deficiency (3.02%) stagnation of qi and blood stasis (2.55%), qi and blood deficiency (2.32%) phlegm-dampness retention (2.32%), blood stasis (2.32%), liver and kidney deficiency (2.08).(2) For the five categories of male infertility,61kinds of medicinals were involved in the treatment,28kinds of them were tonics,12kinds were antipyretics,8kinds were diuretics and dampness-excreting,5kinds act to activate blood,3kinds were astringents,2kinds were inner-warming medicinals and1was for anti-rheumatism and inducing resuscitation. The most significant medicinal herbs for the five male infertility syndromes were epimedium, prepared rhizome of rehmannia, dodder, dogwood and Chinese yam; those for the four male infertility syndromes were poria, cistanche and plantago, medlar; angelica, radix rehmanniae, schisandra chinensis, antler and astragalus root; those for three male infertility syndromes were phellodendron bark and anemarrhena.(3) Out of39literature,15passages were about special formulas,5were about integrated therapy of TCM and Western medicine.①In the19passages for syndrome differentiation and treatment, the top5syndromes were as follows:kidney-yin deficiency, dampness-heat diffusing down type, kidney-yang deficiency, phlegm-accumulation type, kidney-yin deficiency and dampness-heat diffusing down type, The treatment was given based on syndrome differentiation and the complex pathogenesis. The high frequency of traditional Chinese medicine category in the15passages for TCM special formulas and5for integrated therapy of TCM and Western medicine were as follows, nourishing yin and clearing heat, cooling blood to remove blood stasis, clearing heat and removing dampness, resolving hard lumps. It reflected the fact that for the complex mechanism medicinals tonifying yang such as brevicornum was often used②Differentiation of syndromes and diseases adopted was another important feature. The following methods were often used:reinforcing and reducing excessiveness, and keeping balance between yin and yang.(4) The level of some semen metabolites in infertility male with kidney-yang deficiency were found to be elevated as compared with that in fertility male, including2-Keto-6-aminocaproic acid, Pantothenic Acid,4,6-Dideoxy-4-oxo-dTDP-D-glucose, Taurocholic acid, PGA1, PGA2, PA(21:4), Palmitic acid, Pyroglutamic acid, Pyrroline hydroxycarboxylic acid, and the level of other metabolites was decreased, including2-Phenylacetamide,4-(Glutamylamino) butanoate, C16Sphinganine, C17Sphinganine, Clupanodonic acid, Deoxycholic acid, Docosenamide, Mannitol, N-palmitoyl alanine, Oleamide, PGE2, Phenylpyruvic acid, Sphinganine, Tyrosine, UDP-N-acetyl-D-galactosamine,5’-Phosphoribosyl-N-formylglycinamide, Hypoxanthine,6-Keto-PGFl α/TXB2, Aconitic acid, APS/ADP/dGDP, CDP-4-dehydro-3,6-dideoxy-D-glucose, CDP-ethanolamine, Citraconic acid, Citramalic acid, Citric acid, Dehydroascorbic acid, Furoic acid, Glutaconic acid, Homovanillic acid, PS(20:4), thymidine glycol, and Tyrosine.[Conclusions](1) Although the syndrome distribution in male infertility has been reported disorderly and inconsistently, the syndrome elements extracted with relatively low number show that the disorder is in the kidney, spleen and lower jiao, and the main cause is yang deficiency, yin deficiency and essence deficiency. Besides, stasis of blood, dampness-heat and consumption might also be the important reason of male infertility. The study will provide some references for establishing syndrome differentiation criteria and guiding clinical work.(2) Various kinds of traditional Chinese formula have been applied in the treatment of male infertility, furthermore, most of them are concentrated on categories of tonics, antipyretics, nourishment and activation of blood and removal of dampness, which means that in treatment we have to consider reinforcing and reducing, strengthening yin and yang and healthy qi to eliminate pathogens.(3) The disease mechanism of male infertility is complicated, because it sometimes results from semen non-liquefaction, mingled with excess and deficiency syndromes. Syndromes such as kidney-yang deficiency, kidney-yin deficiency, dampness-heat in the lower jiao, phlegm-accumulation, blood stasis are often seen in these patients. It is necessary to weigh and consider balance between insufficiency and excessiveness when the scheme of treatment is decided.(4) There is significant difference in semen metabolites between infertility male with kidney-yang deficiency and fertility male. Patients with kidney-yang deficiency show great changes in metabolic pathways of organic acids and lipids.