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Infertility caused by diabetes is rescued!Salva is actually this ingredient of traditional Chinese medicine

Diabetes (DM) is a chronic metabolic disease characterized by high blood glucose. In recent years, the incidence of diabetes has risen rapidly. Due to the complexity and severe diabetic complications, it has become one of the main causes of death in patients with diabetes, which seriously threatens the health and socioeconomic economy of the world. Among them, the incidence of diabetes is also closely related to infertility. More and more young people, even children, have been diagnosed with type 2 diabetes.

In addition, more and more evidence shows that diabetic hyperglycemia can widely damage the male reproductive system and accompanied by severe testicular tissue damage, including destruction of tubing tubes and sperm generic disorders, decreased serum hormones, oxidation stress and withering in testicles in testicles Increased death. However, the potential mechanism of male reproductive damage caused by diabetes is still not completely clear, and there is currently no effective treatment strategy or drug.

At present, the screening of effective candidates for Chinese medicine has attracted more and more attention. Among them, Icarin (ica) is the main active ingredient of Epimedium, which is traditionally used to treat erectile dysfunction. Studies have pointed out that an appropriate amount of ICA can increase the expression of testosterone secretion by increasing the expression of follicular stimulating hormone receptors (FSHR) and. As a result, sperm occurs.

In addition, NAN and others have discovered that ICA can stimulate cell proliferation and play an important role in regulating the self -update and differentiation of stem cell stem cells. ICA can also improve the male reproductive function by regulating the lower mound-pituitary-gland (HPG) shaft.

Recent research also shows that ICA also has anti -apoptosis in other systems. It is reported that ICA reduces the oxidation stress of myocardial cells; qiao et al. Found that ICA can reduce the kidney toxicity induced by cisplatin by inhibiting mitochondrial dependencies before treatment. Wang et al. Discover ICA to enhance neuronal vitality and reduce neuron death. Zhao et al. Confirmed that ICA can inhibit AGE -induced PC12 cell damage through a specific targeting BAX, thereby regulating mitochondrial apoptosis. These studies show that the anti -apoptosis of ICA is closely related to classic mitochondrial apoptosis pathways.

Therefore, there are reason to speculate that mitochondrial apoptosis can participate in the protection of ICA on male reproductive systems. However, the impact of ICA on the male reproductive dysfunction of diabetic rats and its mechanisms are unclear. In this study, by establishing a high -fat diet (HFD) and the diabetic rats -induced diabetic rats, compared with the dual -dual -tadpoles, the protection role of ICA on the testicular dysfunction of testicular dysfunction is evaluated. The impact of the proliferation and apoptosis of rat testicular cells.

1. ICA improved the parameters of diabetes of diabetic rats

The T2DM rats model was successfully established according to the DM diagnostic standard. The weight of diabetic rats decreases significantly, and FBG, FINS and insulin resistance index (IRI) increase. To test the role of ICA, detect the above parameters of ICA treatment of diabetes rats. ICA processing significantly reduces FBG and IRI, but has no effect on weight and FINS. As a first -line drug to manage hyperglycemia, the dual -dual -dual -dual -duplex is used as a comparative group to evaluate the efficiency of ICA. The two -metal dual -tadpole group increased weight and FINS and reduced FBG and IRI. The results of hormone analysis show that the blood level of T2DM testosterone, LH, and FSH is significantly lower than the control group; compared with the T2DM group, both the dual -two and ICA drug groups restore sex hormone levels.

2. ICA relieves diabetic rats testoship dysfunction

Previous studies have confirmed the causal relationship between DM and male reproductive dysfunction. In order to determine the protective role of ICA on male reproductive functions, we first detected testicular weight, epididymal weight, sperm quantity and sperm vitality. Compared with the T2DM group, the four parameters of the two -meta dual -dual -dual group and the ICA group have obvious recovery, but the increase in the number of sperm in the ICA group is not as good as that of the two -meta group.

Then further check the organizational structure. T2DM group transfusion small tubes severely shrank to thin walls, and the cross -sectional area of ​​spermoscope pipes was significantly reduced. In the abnormal essence epithelium, the number of sperm cells, primary sperm cells and support cells supports a significant reduction, and a small amount of sperm can be seen in the cavity. Among the two -metal dual -dual -dual -dual -dual -dual -dual -dual -dual -duplex and ICA group, the historians of male diabetes rats have been significantly repaired, especially the number of sperm cells, primary female cells, and the number of supporting cells.

3. The expression of the ica increases PCNA

In addition, we have also studied the distribution and expression of the proliferative cells (PCNA), which plays a vital role in the distribution and expression of the antigen in the balance of cell survival and death. The results show that PCNA dyeing can be detected in almost all raw sperm cells and support cells. The strongest area of ​​PCNA dyeing is the peripheral area of ​​the fine tube. Mainly. T2DM group PCNA -positive cells) and PCNA mRNA expression volumes) were significantly reduced and lowered, respectively. After ICA processing, PCNA signals and PCNA positive cells increased significantly. PCNA’s MRNA expression has also been significantly increased. Compared with ICA, the dual -dual -tadpoles show similar effects.

In addition, QPCR results indicate that compared with the control group, the mRNA expression level of the type 2 diabetic group’s peroxide (CAT), glutathione peroxidase (GPX), and the MRNA expression of the super oxide dismissal (SOD) And both the two -metal and ICA treatment are partially restored the MRNA expression level of GPX and SOD in the testicles of diabetic rats (Figure 4).

4. ICA activates SIRT1 -HIF -1α axis

More and more studies have shown that one of the most studied acelase, SIRT1, plays an important role in sperm occurrence and male reproductive functions. There is obvious correlation between SIRT1 and insulin resistance. In addition, SIRT1 can directly remove acetylization and stabilize HIF-1α. HIF-1α is a transcription regulatory factor with hypoxia activation that can regulate the transcription reaction of hypoxia response factor to protect the sperm cells in the testicles from apoptosis. These studies suggest that the SIRT1-HIF-1α axis plays an important role in repairing DM-induced male reproductive dysfunction.

Therefore, this study further detects the activity of the SIRT1-HIF-1α shaft. In the T2DM group, the number of positive and HIF-1α-positive cells in SIRT1 is reduced. QRT-PCR and Western Blotting analysis shows that both SIRT1 and HIF-1α are lowered (Figure 5B, D and E). In contrast, ICA or dual-dual-dual-dual-bearing can clearly reverse these situations, which not only enhances the signals of SIRT1 and HIF-1α, but also increase the expression of SIRT1 and HIF-1α.

5. ICA reduces diabetic mice mitochondria apoptosis signals

The normal development of reproductive cells and reproductive systems depends on the balancing of mitochondrial apoptosis on the BCL-2 family protein. Studies have confirmed that ICA anti-apoptosis is closely related to the BCL-2 signaling pathway. Therefore, this study also conducted Tune experiments to identify the expression of the genes related to the genes of mitochondria apoptosis pathways, BCL-2, BAX, and Caspase-3. Compared with the control group, the number of apoptotic cells in the tubes of the T2DM group increased significantly, and the apoptosis signal was mainly concentrated in the perimeter area. The MRNA expression of BCL-2, BAX, and Caspase-3 has been significantly lowered.

In contrast, the number of apoptotic cells in the ICA group and the two-meta group decreased significantly, and the expression of BCL-2, BAX and Caspase-3 MRNA was significantly up and down, especially the ICA group was significantly reduced.

<!-2586: Diabetic terminal page

In general, this study revealed that ICA may prevent DM -induced testeous dysfunctional dysfunction by enhancing cell proliferation and inhibitory mitochondria dependencies. The results of this study show that ICA can effectively reduce DM -induced male reproductive dysfunction and sperm defects. ICA may improve DM -induced sperm defects by increasing the proliferation of sperm cells, primary ejacula cells and supporting cells to support the proliferation of mitochondria. The results of this study show that ICA may be a new type of treatment drugs that protect and treat SM -induced testicular injuries.

Original source:

He et al.Icariin improves testicular dysfunction via enhancing proliferation and inhibiting mitochondria-dependent apoptosis pathway in high-fat diet and streptozotocin-induced diabetic rats. Reproductive Biology and Endocrinology (2021) 19:168.https://doi.org/10.1186 /S12958-021-00851-9

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