| Popis: |
Wound healing is a process through which all damaged tissues attempt to establish structural integrity and normal functioning. There are many factors / pathological entities that can create difficulties in the wound healing process; several complications, particularly the state of ischemia. Patients with ischemic wounds are often exposed to long and painful treatments, which in some cases unfortunately result in amputation or even death, particularly when all known wound healing treatment methods fail their task. Considering that there are still no adequate pharmacological cures or surgical methods to face such situations, further scientific research is necessary in order to discover a new way to safely and effectively help wound healing and eliminate possible complications, either cause or consequence in the healing process. As an answer to this problem, we present the pentadecapeptide BPC 157: a strong peptide that features unique characteristics and unlike other peptides does not need a carrier. It has been recognised as the basic protective factor in saliva and gastric juices and is extremely safe (there has been no record of lethal doses) and stable (stable in gastric juices for a period of time of over 24 hours). Its positive effect in the healing of lesions of different tissues and organ systems, such as skin, muscles, tendons, ligaments, neural tissue, bones, gastrointestinal system tissues and blood vessels, has been proved in many scientific studies. Moreover, it has been proved that the BPC 157 interacts with many systems in the organism, particularly the NO system. In addition, their interactions in ischemic conditions have been investigated, but simultaneous effect on wound healing in such circumstances has not been recorded. The purpose of this study is to prove that the administration of pentadecapeptide BCP 157 results in quick wound healing in circumstances of induced ischemia of the hind limbs, during the permanent ligation of the common iliac artery, and that this phenomenon is mediated by the action of the NO system. In this research, we have implemented a rat model of wound healing in induced ischemic conditions of the hind limbs, during the permanent ligation of the common iliac artery. The experiment was carried out on 255 male Wistar Albino rats with body mass between 350 g and 450 g, kept in normal conditions with at least 5 rats per experimental group and time period. On the rats, we made a permanent ligation of the left common iliac artery and then we inflicted a wound on the skin of the left hind limb. After the rats were randomly distributed in 11 groups (of 5 rats in each group or subgroup), they were treated relatively to each group with a 0,9% NaCl solution, drinking water, neutral cream (Belobaza), pentadecapeptide BPC 157 in doses of micrograms and nanograms (intraperitoneal and oral administration, and local administration in cream form), L-arginin (intraperitoneally) and L-NAME (intraperitoneally) and with their mutual combinations. Then, a histological examination was conducted on the tissue samples from the ischemic wound of the left hind limb, after which a macroscopic examination of the ischemic wound was conducted as well as a functional examination of the ischemia of the left hind limb. All macroscopic, functional and histologica examinations were conducted in experimental time periods of 24 hours, 3 days, 7 days, 14 days and 21 days, according to former studies. The research showed that the pentadecapeptide BPC 157 speeds up the healing process in unfavourable conditions (ischemia) and proved that it reduces the induced ischemia of the rats hind limb bringing the ischemicised limbs to a state of complete blood flow. In all experimental time periods, the wound featured a smaller area, a better and higher contractility and lower edges. Eventually, when compared to the control group, the wounds on all animals were completely healed, with no complications whatsoever. Also, despite severe induced ischaemia, the status of hind limb ischaemia was promptly reduced and almost completely gone within 24 hrs. Besides, changes that undoubtedly point out the effect of the NO system on the tissue healing process (in this case of an ischemic wound) were observed following the administration of BPC 157, L-arginine and L-NAME, and their mutual combinations. The combination of the pentadecapeptide BPC 157 and L-arginine strengthened the otherwise mild positive effect of Larginine. Moreover, the negative effect of L-NAME (difficult and slower wound healing in comparison to the control group) was annulled by the effect of L-arginine and vice versa (LNAME + L-arginine reached control level), whereas the administration of BPC 157, besides annulling the negative effect of L-NAME, not only brought its damaging effect to regression but also resulted in a positive effect in the wound healing process (L-NAME+BPC 157, LNAME+ L-arginine+BPC 157 resulted in a reduction below control level). All mentioned positive effects of the BPC 157 were achieved regardless of the dose (micrograms or nanograms) and administration modality (per i.p,, per os. and local administration). Our study furthermore shows that the use of the pentadecapeptide BPC 157 in the treatment of ischemic ulcus of rats' skin (ischemic wound) in both doses and in all administration modalities (intraperitoneally, perorally and locally) significantly improves the healing. A similar effected was partially noticed in the administration of L-arginine, whereas an opposite effect was achieved by administrating L-NAME. We hereby point out the fact that the NO system undoubtedly contributes to the healing of ischemic wounds of the skin (ischemic ulcus) and that a positive effect of the pentadecapeptide BPC 157 in the healing of ischemic wounds of the skin is mediated by the action of the NO system. |
